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1.
J Med Virol ; 95(1): e28130, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36068377

RESUMEN

Due to the adverse effects of obesity on host immunity, this study investigated the effectiveness of COVID-19 vaccines (BNT162b2, ChAdOx-nCov-2019, and mRNA-1273) in inducing anti-SARS-CoV-2 Spike (S) neutralizing antibodies among individuals with various obesity classes (class I, II, III, and super obesity). Sera from vaccinated obese individuals (n = 73) and normal BMI controls (n = 46) were subjected to S-based enzyme-linked immunosorbent assay (ELISA) and serum-neutralization test (SNT) to determine the prevalence and titer of anti-SARS-CoV-2 neutralizing antibodies. Nucleocapsid-ELISA was also utilized to distinguish between immunity acquired via vaccination only versus vaccination plus recovery from infection. Data were linked to participant demographics including age, gender, past COVID-19 diagnosis, and COVID-19 vaccination profile. S-based ELISA demonstrated high seroprevalence rates (>97%) in the study and control groups whether samples with evidence of past infection were included or excluded. Interestingly, however, SNT demonstrated a slightly significant reduction in both the rate and titer of anti-SARS-CoV-2 neutralizing antibodies among vaccinated obese individuals (60/73; 82.19%) compared to controls (45/46; 97.83%). The observed reduction in COVID-19 vaccine-induced neutralizing humoral immunity among obese individuals occurs independently of gender, recovery from past infection, and period from last vaccination. Our data suggest that COVID-19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which highlight the importance of booster doses to improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID-19 vaccine effectiveness on humoral immunity induction.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de COVID-19 , Inmunidad Humoral , Estudios Seroepidemiológicos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Obesidad , SARS-CoV-2 , Vacunación
2.
Clin Lab ; 69(2)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36787548

RESUMEN

BACKGROUND: Testing of blood donors for markers of transfusion-transmitted infections (TTIs) such as HBV, HCV, HIV, HTLV, syphilis, and malaria is mandatory in Saudi Arabia. This study determined the prevalence of all tested TTIs among blood donors in the western region of Saudi Arabia. METHODS: This retrospective study included 5,473 blood donors who attended the blood donation center at the Security Force Hospital (SFH) located in the western region of Saudi Arabia from January 1, 2015 to December 31, 2018. The prevalence of TTIs was determined and classified as per year, gender, age, type of donors (first-time vs. returned donors), category of donation (replacement vs. volunteer), and blood group. RESULTS: All donors (100%) were screened for TTIs by serological assays and nucleic acid tests (NATs). "Reactive" samples to serological assays were as follow: 57 (1.07%) HBsAg, 292 (5.34%) HBsAb, 388 (7.1%) HBcAbs, 13 (0.24%) HCV, 5 (0.09%) HIV, 8 (0.15%) HTLV-I and -II, 21 (0.83%) syphilis, and 0 (0%) malaria. The NAT results for HBV, HCV, and HIV revealed 50 (0.91%), 1 (0.0002%), and 3 (0.05%) reactive samples, respectively. Reactive donations to screening serology tests of syphilis and HTLV-I/-II were neither confirmed nor declined by their corresponding confirmatory assays. Most "reactive" samples to TTI tests were associated with male gender, first-time donor, replacement donation, and O+ blood group. CONCLUSIONS: This study highlights the strong adherence to TTI testing policy and low prevalence of TTI markers among blood donors in the western region of Saudi Arabia.


Asunto(s)
Antígenos de Grupos Sanguíneos , Infecciones por VIH , Hepatitis C , Sífilis , Reacción a la Transfusión , Humanos , Masculino , Donantes de Sangre , Sífilis/diagnóstico , Sífilis/epidemiología , Prevalencia , Estudios Retrospectivos , Arabia Saudita/epidemiología , Reacción a la Transfusión/epidemiología , Hospitales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología
3.
Mar Drugs ; 21(12)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38132947

RESUMEN

Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused b a special type of coronavirus called MERS-CoV. In the search for effective substances against the MERS-CoV main protease, we looked into compounds from brown algae, known for their medicinal benefits. From a set of 1212 such compounds, our computer-based screening highlighted four-CMNPD27819, CMNPD1843, CMNPD4184, and CMNPD3156. These showed good potential in how they might attach to the MERS-CoV protease, comparable to a known inhibitor. We confirmed these results with multiple computer tests. Studies on the dynamics and steadiness of these compounds with the MERS-CoV protease were performed using molecular dynamics (MD) simulations. Metrics like RMSD and RMSF showed their stability. We also studied how these compounds and the protease interact in detail. An analysis technique, PCA, showed changes in atomic positions over time. Overall, our computer studies suggest brown algae compounds could be valuable in fighting MERS. However, experimental validation is needed to prove their real-world effectiveness.


Asunto(s)
Infecciones por Coronavirus , Coronavirus del Síndrome Respiratorio de Oriente Medio , Humanos , Proteínas Virales , Infecciones por Coronavirus/tratamiento farmacológico , Endopeptidasas , Péptido Hidrolasas/farmacología
4.
Molecules ; 27(8)2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35458761

RESUMEN

Zika virus (ZIKV) has been characterized as one of many potential pathogens and placed under future epidemic outbreaks by the WHO. However, a lack of potential therapeutics can result in an uncontrolled pandemic as with other human pandemic viruses. Therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted a strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the NS2B-NS3 protease (ZIKVpro) and NS5 RNA dependent RNA polymerase (ZIKVRdRp) proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of the top four common bioflavonoids, viz. Rutin, Nicotiflorin, Isoquercitrin, and Hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (B:His51, B:Asp75, and B:Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Besides, long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals stability of the respective docked poses contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp against ZIKV for further experimental assessment.


Asunto(s)
Azadirachta , Infección por el Virus Zika , Virus Zika , Antivirales/química , Azadirachta/química , Flavonoides/química , Humanos , Plomo/farmacología , Simulación del Acoplamiento Molecular , Péptido Hidrolasas/farmacología , Inhibidores de Proteasas/química , ARN Polimerasa Dependiente del ARN , Proteínas no Estructurales Virales/metabolismo , Infección por el Virus Zika/tratamiento farmacológico
5.
Saudi Pharm J ; 30(7): 979-1002, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35637849

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a more severe strain of coronavirus (CoV) that was first emerged in China in 2019. Available antiviral drugs could be repurposed and natural compounds with antiviral activity could be safer and cheaper source of medicine for SARS-CoV-2. 78 natural antiviral compounds database was identified from literature and virtual screening technique was applied to identify potential 3-chymotrypsin-like protease (3CLpro) inhibitors. Molecular docking studies were conducted to analyze the main protease (3CLpro) and inhibitors interactions with key residues of active site of target protein (PDB ID: 6LU7), active site constitute the part of active domain I and II of 3CLpro. 10 compounds with highest dock score were subjected to calculate ADMET parameters to figure out drug-likeness. Molecular dynamic (MD) simulation of the selected lead was performed by Amber simulation package to understand the conformational changes in docked complex. MD simulations analysis (RMSD, RMSF, Rg, BF, HBs, and SASA plots) of lead bounded with 3CLpro, hence revealed the important structural turns and twists during MD simulations from 0 to 100 ns. MM-PBSA/GBSA methods has also been applied for the estimation binding free energy (BFE) of the selected lead-complex. The present study has identified lead compound "Forsythoside A" an active extract of Forsythia suspense as SARS-CoV-2 3CLpro inhibitor that can block the viral replication and translation. Structural analysis of target protein and lead compound performed in this study could contribute to the development of potential drug against SARS-CoV-2 infection.

6.
Vox Sang ; 116(6): 673-681, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33277935

RESUMEN

BACKGROUND AND OBJECTIVES: During the ongoing pandemic of COVID-19, SARS-CoV-2 RNA was detected in plasma and platelet products from asymptomatic blood donors, raising concerns about potential risk of transfusion transmission, also in the context of the current therapeutic approach utilizing plasma from convalescent donors. The objective of this study was to assess the efficacy of amotosalen/UVA light treatment to inactivate SARS-CoV-2 in human plasma to reduce the risk of potential transmission through blood transfusion. METHODS: Pools of three whole-blood-derived human plasma units (630-650 ml) were inoculated with a clinical SARS-CoV-2 isolate. Spiked units were treated with amotosalen/UVA light (INTERCEPT Blood System™) to inactivate SARS-CoV-2. Infectious titres and genomic viral load were assessed by plaque assay and real-time quantitative PCR. Inactivated samples were subject to three successive passages on permissive tissue culture to exclude the presence of replication-competent viral particles. RESULTS: Inactivation of infectious viral particles in spiked plasma units below the limit of detection was achieved by amotosalen/UVA light treatment with a mean log reduction of >3·32 ± 0·2. Passaging of inactivated samples on permissive tissue showed no viral replication even after 9 days of incubation and three passages, confirming complete inactivation. The treatment also inhibited NAT detection by nucleic acid modification with a mean log reduction of 2·92 ± 0·87 PFU genomic equivalents. CONCLUSION: Amotosalen/UVA light treatment of SARS-CoV-2 spiked human plasma units efficiently and completely inactivated >3·32 ± 0·2 log of SARS-CoV-2 infectivity, showing that such treatment could minimize the risk of transfusion-related SARS-CoV-2 transmission.


Asunto(s)
Furocumarinas/farmacología , Plasma/virología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/efectos de la radiación , Terapia Ultravioleta , Inactivación de Virus , COVID-19/prevención & control , COVID-19/transmisión , Humanos , Reacción a la Transfusión/prevención & control , Resultado del Tratamiento
7.
J Infect Public Health ; 17 Suppl 1: 42-48, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37085376

RESUMEN

Respiratory viral infections pose a public health concern during mass gathering (MG) events. Sustainable and continuous surveillance of respiratory viruses remains a priority to early identify and prevent potential outbreaks. This article reviews recent literature addressed the prevalence and diversity of circulating respiratory viruses during Hajj pilgrimage, one of the largest planned religious MG events held annually in Saudi Arabia. The variation between studies with respect to study design, sample size, time of sample collection (pre-, during, and pos-Hajj), type of participants (e.g., symptomatic vs. a symptomatic pilgrims), and laboratory procedure was highlighted. The majority of these studies were conducted on the 2019 Hajj season or earlier, prior to the emergence of COVID-19 which had significant impact on the past three Hajj seasons (2020, 2021, and 2022). A summary about key aspects related to organization of Hajj during COVID-19 pandemic and the implementation of exceptional infection control strategies is provided.


Asunto(s)
Infecciones del Sistema Respiratorio , Virosis , Virus , Humanos , Estaciones del Año , Pandemias/prevención & control , Viaje , Islamismo , Arabia Saudita/epidemiología , Virosis/epidemiología , Virosis/prevención & control , Infecciones del Sistema Respiratorio/epidemiología
8.
Heliyon ; 10(1): e23027, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38163192

RESUMEN

The risk of transmission of respiratory tract infections is considerably enhanced at mass gathering (MG) religious events. Hajj is an annual Islamic MG event with approximately 3 million Muslim pilgrims from over 180 countries concentrated in Makkah, Saudi Arabia. This study aimed to investigate the genetic diversity of influenza viruses circulating among pilgrims during the Hajj pilgrimage. We performed a cross-sectional analytical study where nasopharyngeal swabs (NPs) from pilgrims with respiratory tract illnesses presenting to healthcare facilities during the 2019 Hajj were screened for influenza viruses. Influenza A subtypes and influenza B lineages were determined by multiplex RT-PCR for positive influenza samples. The phylogenetic analysis was carried out for the hemagglutination (HA) gene. Out of 185 nasopharyngeal samples, 54 were positive for the human influenza virus. Of these, 27 were influenza A H1N1 and 19 H3N2, 4 were untypable influenza A, and 4 were influenza B. Phylogenetic analysis revealed that the H1N1 and H3N2 strains differentiated into different and independent genetic groups and formed close clusters with selected strains of influenza viruses from various locations. To conclude, this study demonstrates a high genetic diversity of circulating influenza A subtypes among pilgrims during the Hajj Season. There is a need for further larger studies to investigate in-depth the genetic characteristics of influenza viruses and other respiratory viruses during Hajj seasons.

9.
Viruses ; 15(1)2023 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-36680291

RESUMEN

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of -10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤-8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of -61.42 kcal/mol and -61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = -53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.


Asunto(s)
Antivirales , Productos Biológicos , Monkeypox virus , Humanos , Inhibidores de Cisteína Proteinasa , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mpox , Monkeypox virus/efectos de los fármacos , Péptido Hidrolasas , Productos Biológicos/farmacología , Antivirales/farmacología
10.
Toxics ; 11(2)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36851040

RESUMEN

During the COVID-19 pandemic, governments in many countries worldwide, including India, imposed several restriction measures, including lockdowns, to prevent the spread of the infection. COVID-19 lockdowns led to a reduction in gaseous and particulate pollutants in ambient air. In the present study, we investigated the substantial changes in selected volatile organic compounds (VOCs) after the outbreak of the coronavirus pandemic and associations with health risk assessments in industrial areas. VOC data from 1 January 2019 to 31 December 2021 were collected from the Central Pollution Control Board (CPCB) website, to identify percentage changes in VOC levels before, during, and after COVID-19. The mean TVOC levels at all monitoring stations were 47.22 ± 30.15, 37.19 ± 37.19, and 32.81 ± 32.81 µg/m3 for 2019, 2020, and 2021, respectively. As a result, the TVOC levels gradually declined in consecutive years due to the pandemic in India. The mean TVOC levels at all monitoring stations declined from 9 to 61% during the pandemic period as compared with the pre-pandemic period. In the current study, the T/B ratio values ranged from 2.16 (PG) to 26.38 (NL), which indicated that the major pollutant contributors were traffic and non-traffic sources during the pre-pandemic period. The present findings indicated that TVOC levels had positive but low correlations with SR, BP, RF, and WD, with correlation coefficients (r) of 0.034, 0.118, 0.012, and 0.007, respectively, whereas negative correlations were observed with AT and WS, with correlation coefficients (r) of -0.168 and -0.150, respectively. The lifetime cancer risk (LCR) value for benzene was reported to be higher in children, followed by females and males, for the pre-pandemic, pandemic, and post-pandemic periods. A nationwide scale-up of this study's findings might be useful in formulating future air pollution reduction policies associated with a reduction in health risk factors. Furthermore, the present study provides baseline data for future studies on the impacts of anthropogenic activities on the air quality of a region.

11.
Vaccines (Basel) ; 11(2)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36851205

RESUMEN

Iron is a crucial micronutrient for immunity induction in response to infections and vaccinations. This study aimed to investigate the effect of iron deficiency on COVID-19-vaccine-induced humoral immunity. We investigated the effectiveness of COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx nCov-2019) in iron-deficient individuals (n = 63) and provide a side-by-side comparison to healthy controls (n = 67). The presence of anti-SARS-CoV-2 spike (S) and anti-nucleocapsid (NP) IgG were assessed using in-house S- and NP-based ELISA followed by serum neutralization test (SNT). High concordance between S-based ELISA and SNT results was observed. The prevalence of neutralizing antibodies was 95.24% (60/63) in the study group and 95.52% (64/67) in the controls with no significant difference. The presence/absence of past infection, period since vaccination, vaccine type, and being iron-deficient or having iron-deficiency anemia did not exert any significant effect on the prevalence or titer of anti-SARS-CoV-2 neutralizing antibodies. NP-based ELISA identified individuals unaware of exposure to SARS-CoV-2. Moreover, absence of anti-NP IgG was noted in participants who were previously diagnosed with COVID-19 suggesting the unpredictability of after-infection immunity. To sum up, this study demonstrated an initial lack of evidence on the association between iron deficiency and the effectiveness of COVID-19-vaccine-induced neutralizing humoral immunity. Similar studies with larger sample size remain necessary to obtain comprehensive conclusions about the effect or lack of effect of iron on COVID-19-vaccine effectiveness.

12.
Sci Rep ; 13(1): 14570, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37666979

RESUMEN

Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of - 8.88 and - 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of - 10.60 and - 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein-ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection.


Asunto(s)
Monkeypox virus , Mpox , Humanos , Reposicionamiento de Medicamentos , Antibacterianos/farmacología , Tetraciclina/farmacología , Minociclina , Descubrimiento de Drogas , Péptido Hidrolasas
13.
Viruses ; 15(8)2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37632081

RESUMEN

The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <-6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (-22.89 kcal/mol), surpassing the control compound's binding energy (-9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.


Asunto(s)
Ebolavirus , Marburgvirus , Quimioinformática , Palmitato de Paliperidona , Biblioteca de Genes
14.
Viruses ; 15(7)2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37515188

RESUMEN

The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public's health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of -77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactions when these chemical complexes were evaluated further under a 100 ns molecular dynamics simulation. Compound 127042987 displayed the best binding free energy (GBind) of -96.50 kcal/mol, surpassing the native ligand binding energy (-66.17 kcal/mole). Thereafter, an MM/GBSA binding free energy study was conducted to validate the stability of selected chemical complexes. Overall, this study illustrated that compound 127042987 showed preferred binding free energies, suggesting a possible inhibitory mechanism against ZIKV-RdRp. As per this study, it was proposed that compound 127042987 could be used as a therapeutic option to prevent Zika virus infection. These compounds need to be tested in experiments for further validation.


Asunto(s)
Infección por el Virus Zika , Virus Zika , Humanos , Virus Zika/genética , Antivirales/química , ARN Polimerasa Dependiente del ARN/genética , Infección por el Virus Zika/tratamiento farmacológico , Simulación de Dinámica Molecular , Simulación del Acoplamiento Molecular
15.
J Biomol Struct Dyn ; : 1-17, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37811742

RESUMEN

Japanese encephalitis (JE), a neurological infection of severe nature, is caused by the Japanese encephalitis virus (JEV) and is transmitted by the mosquito vector. The polymerase domain of Non-structural 5 (NS5), which is also referred to as RdRp (RNA-dependent RNA polymerase), is considered a potential therapeutic target for JEV. The present study employed molecular dynamics modelling and high-throughput virtual screening to evaluate the possible antiviral activity of anti-dengue drugs against JEV RdRp. Furthermore, a ranking was performed utilising the MM/GBSA analysis to identify the three most promising compounds. Compound ID 57409246 exhibited the highest binding affinity with the protein, as evidenced by its minimum binding free energy of -72.96 kcal/mole. In contrast, the other two compounds had minimum binding free energies of -67.57 and -59.19 kcal/mole, respectively. Upon conducting a 100 nanosecond molecular dynamics simulation to confirm the binding of the chemical complexes, it was observed that the three hits, namely 57409246, 70683874, and 44577154, exhibited a consistent and stable RMSD. Subsequently, the binding strength of the trajectory was confirmed through MM/GBSA analysis. The compounds 70683874 and 57409246 exhibited the lowest binding free energies, which were -97.58 kcal/mol and -96.38 kcal/mol, respectively. The binding free energy (ΔG Bind) values for the native ligand ATP and molecule 44577154 were -65.64 kcal/mol and -69.44 kcal/mol, respectively. Overall, compared to the native ligand ATP, all three compounds exhibited higher binding affinity. The study proposes three anti-dengue molecules as a potential remedy for JE, which can be confirmed through in vitro and in vivo investigations.Communicated by Ramaswamy H. Sarma.

16.
Viruses ; 15(2)2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-36851698

RESUMEN

BACKGROUND: The Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Little is known about the seroprevalence of HEV in the general population of Saudi Arabia. METHODS: A community-based cross-sectional HEV seroprevalence study was conducted in Makkah, Saudi Arabia. Anti-HEV IgG antibodies were detected in sera using an in-house ELISA. The frequency of HEV sageerology and its correlation with demographic, and environmental factors were evaluated. RESULTS: Enrollment consisted of 1329 individuals, ages ranged from 8 to 88 years, the mean age was 30.17 years, the median age was 28yrs, and the male: female ratio was 1.15. The overall seroprevalence was 23.8% (316/1329). Males had significantly higher seroprevalence than females (66.1 vs. 33.9%; p < 0.001). Seroprevalence had significant correlations with age, occupation, and lack of regular water supply and housing conditions. CONCLUSIONS: This is the first HEV community-based seroprevalence study from Saudi Arabia. Results show that the HEV is endemic in Makkah and affects all age groups and occupations. HEV affects more males than females and those living in crowded accommodations without a regular supply of water. Further studies are required across all regions of Saudi Arabia to determine the country's seroprevalence of active or past infection using tests for HEV IgG, HEV IgM antibodies and/or HEV RNA and underlying determinants of transmission.


Asunto(s)
Virus de la Hepatitis E , Humanos , Femenino , Masculino , Adulto , Niño , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Arabia Saudita/epidemiología , Estudios Transversales , Estudios Seroepidemiológicos , Anticuerpos Antihepatitis , Inmunoglobulina G
17.
One Health ; 17: 100601, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37520847

RESUMEN

High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and Toscana virus (TOSV) are two of these viruses commonly transmitted by Phlebotomus sandflies. While SFSV can cause rapidly resolving mild febrile illness, TOSV could involve the central nervous system (CNS), causing diseases ranging from aseptic meningitis to meningoencephalitis. Sandfly-associated phleboviruses have not been investigated before in Saudi Arabia and are potential causes of infection given the prevalence of sandflies in the country. Here, we investigated the seroprevalence of SFSV and TOSV in the western region of Saudi Arabia in samples collected from blood donors, livestock animals, and animal handlers. An overall seroprevalence of 9.4% and 0.8% was found in humans for SFSV and TOSV, respectively. Seropositivity was significantly higher in non-Saudis compared to Saudis and increased significantly with age especially for SFSV. The highest seropositivity rate was among samples collected from animal handlers. Specifically, in blood donors, 6.4% and 0.7% tested positive for SFSV and TOSV nAbs, respectively. Animal handlers showed higher seroprevalence rates of 16% and 1% for anti-SFSV and anti-TOSV nAbs, respectively, suggesting that contact with livestock animals could be a risk factor. Indeed, sera from livestock animals showed seropositivity of 53.3% and 4.4% in cows, 27.5% and 7.8% in sheep, 2.2% and 0.0% in goats, and 10.0% and 2.3% in camels for SFSV and TOSV, respectively. Together, these results suggest that both SFSV and TOSV are circulating in the western region of Saudi Arabia in humans and livestock animals, albeit at different rates, and that age and contact with livestock animals could represent risk factors for infection with these viruses.

18.
Diagnostics (Basel) ; 12(4)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35453876

RESUMEN

Background: The global pandemic coronavirus SARS-CoV-2 has a healthcare, social and economic burden. To limit the spread of the virus, the World Health Organization (WHO) urgently called for extensive screening of suspected individuals; thus, a quick, simple, and sensitive diagnostic assay is always in need. Methods: We applied reverse transcription-loop-mediated isothermal amplification (RT-LAMP) for the detection of SARS-CoV-2. The RT-LAMP method was optimized by evaluating two fluorescence amplification mixes and several reaction times, and results were compared to the standard real-time RT-PCR (rtRT-PCR). The assay was validated using 200 nasopharyngeal swabs collected in viral transport media (62 positive for SARS-CoV-2, and 138 negative for SARS-CoV-2 detected by the rtRT-PCR method). The samples were diluted 1:4 in diethylpyrocarbonate (DEPC)-treated water, utilized for RT-LAMP using different singleplex and multiplex sets of LAMP primers (N gene, S gene, and orf1ab gene), and incubated at 65 °C using real-time PCR 7500. Results: Our direct detection with the RT-LAMP protocol showed 100% concordance (sensitivity and specificity) with the standard protocol used for the detection of SARS-CoV-2 nucleic acid. Conclusions: In this study, we set up a rapid, simple, and sensitive RT-LAMP assay for the detection of SARS-CoV-2 in clinical samples. The assay is suitable for point of care detection in public hospitals, medical centers in rural areas, and in transportation hubs.

19.
Int J Infect Dis ; 121: 130-137, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35577249

RESUMEN

OBJECTIVES: Acute respiratory tract infections (ARIs) due to human rhinoviruses (HRVs) are common in pilgrims during the annual Hajj pilgrimage. The objective of this study was to investigate the genetic diversity of HRV among pilgrims with respiratory symptoms during Hajj 2019. METHODS: HRV infection was detected using multiplex real-time reverse transcription polymerase chain reaction. Cycle sequencing was performed on positive samples and the sequences were subjected to phylogenetic analysis. RESULTS: A total of 19 HRV-positive respiratory samples were sequenced. All three serotypes of HRV were identified: HRV-A (13; 68.42%) was more common than HRV-B (2; 10.53%) and HRV-C (4; 21.05%). HRV-A species were found to be of genotypes A101, A21, A30, A57, A23, A60, and A11. HRV-B species belonged to genotypes B4 and B84, and HRV-C species were of genotypes C15, C3, and C56. CONCLUSION: Sequencing studies of respiratory tract viruses in pilgrims are important. We provide preliminary evidence of high diversity of HRV genotypes circulating in pilgrims in a restricted area during Hajj. This requires further clinical and sequencing studies of viral pathogens in larger cohorts of overseas and local pilgrims.


Asunto(s)
Infecciones del Sistema Respiratorio , Rhinovirus , Variación Genética , Humanos , Islamismo , Filogenia , Rhinovirus/genética , Arabia Saudita/epidemiología , Estaciones del Año , Viaje
20.
Comput Biol Chem ; 98: 107645, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35276575

RESUMEN

In this paper, a compartmental mathematical model has been utilized to gain a better insight about the future dynamics of COVID-19. The total human population is divided into eight various compartments including susceptible, exposed, pre-asymptomatic, asymptomatic, symptomatic, quarantined, hospitalized and recovered or removed individuals. The problem was modeled in terms of highly nonlinear coupled system of classical order ordinary differential equations (ODEs) which was further generalized with the Atangana-Balaeanu (ABC) fractional derivative in Caputo sense with nonlocal kernel. Furthermore, some theoretical analyses have been done such as boundedness, positivity, existence and uniqueness of the considered. Disease-free and endemic equilibrium points were also assessed. The basic reproduction was calculated through next generation technique. Due to high risk of infection, in the present study, we have considered the reported cases from three continents namely Americas, Europe, and south-east Asia. The reported cases were considered between 1st May 2021 and 31st July 2021 and on the basis of this data, the spread of infection is predicted for the next 200 days. The graphical solution of the considered nonlinear fractional model was obtained via numerical scheme by implementing the MATLAB software. Based on the fitted values of parameters, the basic reproduction number ℜ0 for the case of America, Asia and Europe were calculated as ℜ0≈2.92819, ℜ0≈2.87970 and ℜ0≈2.23507 respectively. It is also observed that the spread of infection in America is comparatively high followed by Asia and Europe. Moreover, the effect of fractional parameter is shown on the dynamics of spread of infection among different classes. Additionally, the effect of quarantined and treatment of infected individuals is also shown graphically. From the present analysis it is observed that awareness of being quarantine and proper treatment can reduce the infection rate dramatically and a minimal variation in quarantine and treatment rates of infected individuals can lead us to decrease the rate of infection.


Asunto(s)
COVID-19 , Cuarentena , Asia , Número Básico de Reproducción , COVID-19/epidemiología , Hospitalización , Humanos
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