Mechanistic insight and possible mechanism of seizure in Covid-19: The nuances and focal points.

Coronavirus disease 2019 (COVID-19) is a primary respiratory disease with an alarming impact worldwide. COVID-19 is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and presents various neurological symptoms, including seizures. SARS-CoV-2 shows neuroinvasive and neurotropic capabilities through a neuronal angiotensin-converting enzyme 2 (ACE2), which is also highly expressed in both neuronal and glial cells. Therefore, SARS-CoV-2 can trigger neuroinflammation and neuronal hyperexcitability, increasing the risk of seizures'. Olfactory neurons could be an exceptional neuronal pathway for the neuroinvasion of respiratory viruses to access the central nervous system (CNS) from the nasal cavity, leading to neuronal injury and neuroinflammation. Although neuronal ACE2 has been widely studied, other receptors for SARS-CoV-2 in the brain have been proposed to mediate viral-neuronal interactions with subsequent neurological squeals. Thus, the objective of the present critical review was to find the association and mechanistic insight between COVID-19 and the risk of seizures.

Risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination.

BACKGROUND: Severe complications from COVID-19 and poor responses to SARS-CoV-2 vaccination were commonly reported in cancer patients compared to those without cancer. Therefore, the identification of predisposing factors to SARS-CoV-2 infection in cancer patients would assist in the prevention of COVID-19 and improve vaccination strategies. The literature lacks reports on this topic from the Kingdom of Saudi Arabia (KSA). Therefore, we studied clinical and laboratory data of 139 cancer patients from King Abdulaziz Medical City, Riyadh, KSA. METHODS: The cancer patients fall into three categories; (i) uninfected with SARS-CoV-2 pre-vaccination and remained uninfected post-vaccination (control group; n = 114; 81%), (ii) pre-vaccination infected group (n = 16; 11%), or (iii) post-vaccination infected group (n = 9; 6%). Next, the clinical and lab data of the three groups of patients were investigated. RESULTS: Comorbidity factors like diabetes and hemodialysis were associated with the risk of infection in cancer patients before the vaccination (p<0.05). In contrast to breast cancer, papillary thyroid cancer was more prevalent in the infected patients pre- and post-vaccination (p<0.05). Pre-vaccination infected group had earlier cancer stages compared with the control group (p = 0.01). On the other hand, combined therapy was less commonly administrated to the infected groups versus the control group (p<0.05). Neutrophil to lymphocyte ratio was lower in the post-vaccination infected group compared to the control group (p = 0.01). CONCLUSION: Collectively, this is the first study from KSA to report potential risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination. Further investigations on these risk factors in a larger cohort are worthwhile to draw a definitive conclusion about their roles in predisposing cancer patients to the infection.

In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.

Mucormycosis co-infection in COVID-19 patients: An update.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients' co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

Delivery of MERS antigen encapsulated in α-GalCer-bearing liposomes elicits stronger antigen-specific immune responses.

Alpha-Galactosylceramide (α-GalCer) effectively activates the natural killer T (NKT) cells to secrete remarkable amounts of Th1 and Th2 cytokines and therefore, acts as a potential immunoadjuvant in vaccine formulation. In the present study, we prepared α-GalCer-bearing or α-GalCer-free liposomes and loaded them with Middle East Respiratory Syndrome Coronavirus papain-like protease (α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro). These formulations were injected in mice to investigate the antigen-specific humoral and cell-mediated immune responses. The immunisation with α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro did not induce any notable toxicity in immunised mice. The results demonstrated that mice immunised with α-GalCer-Lip-MERS-CoV PLpro showed greater antigen-specific antibody titre, switching of IgG isotyping to IgG2a subclass and higher lymphocyte proliferation. Moreover, the splenocytes from α-GalCer-Lip-MERS-CoV PLpro immunised mice secreted greater levels of IFN-γ, IL-4, IL-2 and IL-12. Interestingly, a booster dose induced stronger memory immune responses in mice previously immunised with α-GalCer-Lip-MERS-CoV PLpro. In summary, α-GalCer-Lip-MERS-CoV PLpro may prove to be a promising vaccine formulation to protect the individuals against MERS-CoV infection.

Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?

Since the start of the COVID-19 pandemic, numerous variants of SARS-CoV-2 have been reported worldwide. The advent of variants of concern (VOCs) raises severe concerns amid the serious containment efforts against COVID-19 that include physical measures, pharmacological repurposing, immunization, and genomic/community surveillance. Omicron variant (B.1.1.529) has been identified as a highly modified, contagious, and crucial variant among the five VOCs of SARS-CoV-2. The increased affinity of the spike protein (S-protein), and host receptor, angiotensin converting enzyme-2 (ACE-2), due to a higher number of mutations in the receptor-binding domain (RBD) of the S-protein has been proposed as the primary reason for the decreased efficacy of majorly available vaccines against the Omicron variant and the increased transmissible nature of the Omicron variant. Because of its significant competitive advantage, the Omicron variant and its sublineages swiftly surpassed other variants to become the dominant circulating lineages in a number of nations. The Omicron variant has been identified as a prevalent strain in the United Kingdom and South Africa. Furthermore, the emergence of recombinant variants through the conjunction of the Omicron variant with other variants or by the mixing of the Omicron variant's sublineages/subvariants poses a major threat to humanity. This raises various issues and hazards regarding the Omicron variant and its sublineages, such as an Omicron variant breakout in susceptible populations among fully vaccinated persons. As a result, understanding the features and genetic implications of this variant is crucial. Hence, we explained in depth the evolution and features of the Omicron variant and analyzed the repercussions of spike mutations on infectiousness, dissemination ability, viral entry mechanism, and immune evasion. We also presented a viewpoint on feasible strategies for precluding and counteracting any future catastrophic emergence and spread of the omicron variant and its sublineages that could result in a detrimental wave of COVID-19 cases.

Persistence of Anti-SARS-CoV-2 Spike IgG Antibodies Following COVID-19 Vaccines.

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

Can the SARS-CoV-2 Omicron Variant Confer Natural Immunity against COVID-19?

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with no signs of abatement in sight. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of this pandemic and has claimed over 5 million lives, is still mutating, resulting in numerous variants. One of the newest variants is Omicron, which shows an increase in its transmissibility, but also reportedly reduces hospitalization rates and shows milder symptoms, such as in those who have been vaccinated. As a result, many believe that Omicron provides a natural vaccination, which is the first step toward ending the COVID-19 pandemic. Based on published research and scientific evidence, we review and discuss how the end of this pandemic is predicted to occur as a result of Omicron variants being surpassed in the community. In light of the findings of our research, we believe that it is most likely true that the Omicron variant is a natural way of vaccinating the masses and slowing the spread of this deadly pandemic. While the mutation that causes the Omicron variant is encouraging, subsequent mutations do not guarantee that the disease it causes will be less severe. As the virus continues to evolve, humans must constantly adapt by increasing their immunity through vaccination.

Bioactive phytoconstituents as potent inhibitors of casein kinase-2: dual implications in cancer and COVID-19 therapeutics.

Casein kinase 2 (CK2) is a conserved serine/threonine-protein kinase involved in hematopoietic cell survival, cell cycle control, DNA repair, and other cellular processes. It plays a significant role in cancer progression and viral infection. CK2 is considered a potential drug target in cancers and COVID-19 therapy. In this study, we have performed a virtual screening of phytoconstituents from the IMPPAT database to identify some potential inhibitors of CK2. The initial filter was the physicochemical properties of the molecules following the Lipinski rule of five. Then binding affinity calculation, PAINS filter, ADMET, and PASS analyses followed by interaction analysis were carried out to discover nontoxic and better hits. Finally, two compounds, stylopine and dehydroevodiamines with appreciable affinity and specific interaction towards CK2, were identified. Their time-evolution analyses were carried out using all-atom molecular dynamics simulation, principal component analysis and free energy landscape. Altogether, we propose that stylopine and dehydroevodiamines can be further explored in in vitro and in vivo settings to develop anticancer and antiviral therapeutics.

Hand Hygiene Knowledge and Perception among the Healthcare Workers during the COVID-19 Pandemic in Qassim, Saudi Arabia: A Cross-Sectional Survey.

Hand hygiene is among the most important factors of infection control in healthcare settings. Healthcare workers are the primary source of hospital-acquired infection. We assessed the current state of hand hygiene knowledge, perception, and practice among the healthcare workers in Qassim, Saudi Arabia. In this cross-sectional study, we used the hand hygiene knowledge and perception questionnaire developed by the World Health Organization. Knowledge and perceptions were classified into good (80-100%), moderate (60-79%), and poor (<60% score). The majority of the healthcare workers had moderate knowledge (57.8%) and perception (73.4%) of hand hygiene. Males were less likely to have moderate/good knowledge compared to females (OR: 0.52, p < 0.05). Private healthcare workers were less likely (OR: 0.33, p < 0.01) to have moderate/good perceptions compared to the government healthcare workers. Healthcare workers who received training on hand hygiene were more likely to have good/moderate perception (OR: 3.2, p < 0.05) and to routinely use alcohol-based hand rubs (OR: 3.8, p < 0.05) than the ones without such training. Physicians are more likely (OR: 4.9, p < 0.05) to routinely use alcohol-based hand rubs than technicians. Our research highlighted gaps in hand hygiene knowledge, perception and practice among healthcare workers in Qassim, Saudi Arabia and the importance of training in this regard.

Haematological and radiological-based prognostic markers of COVID-19.

BACKGROUND: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). METHODS: Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. RESULTS: More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d-dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d-dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d-dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. CONCLUSION: Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients.

Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition.

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.

A computational study on active constituents of Habb-ul-aas and Tabasheer as inhibitors of SARS-CoV-2 main protease.

A respiratory pandemic known as coronavirus disease-19 (COVID-19) has created havoc since it emerged from Wuhan, China. COVID-19 is caused by a newly emerged SARS coronavirus (SARS-CoV) with increased pathogenicity named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the lack of understanding of the mechanism of pathogenesis, an effective therapeutic option is unavailable. Epidemics described in Unani ancient literature include nazla-e-wabai and humma-e-wabai, and most of the symptoms of COVID-19 resemble nazla-e-wabai. Hence, in light of Unani literature, the treatment of COVID-19 can be managed with the composites prescribed in Unani medicine for nazla-e-wabai. In this study, a structure-based drug design approach was carried out to check the effectiveness of the pharmacologically active constituents of the Unani composites prescribed to treat nazla-e-wabai against SARS-CoV-2. We performed molecular docking of the active constituents of these composites against the main protease (Mpro), a potential drug target in SARS-CoV-2. Using detailed molecular docking analysis, Habb-ul-aas and Tabasheer were identified as potential inhibitors of SARS-CoV-2 Mpro. The active constituents of both these composites bind to the substrate-binding pocket of SARS-CoV-2 Mpro, forming interactions with key residues of the binding pocket. Molecular dynamics (MD) simulation suggested the binding of active constituents of Habb-ul-aas with SARS-CoV-2 Mpro with a strong affinity as compared to the constituents of Tabasheer. Thus, this study sheds light on the use of these Unani composites in COVID-19 therapeutics.Communicated by Ramaswamy H. Sarma.

COVID-19 Pandemic: Epidemiology, Etiology, Conventional and Non-Conventional Therapies.

Coronavirus disease 2019 (COVID-19), which reported in an outbreak in 2019 in Wuhan, Hubei province, China, is caused by the SARS-CoV-2 virus. The virus belongs to the beta-coronavirus class, along with the Middle East Respiratory Syndrome coronavirus and Severe Acute Respiratory Syndrome coronavirus. Interestingly, the virus binds with angiotensin-converting enzyme-2 found in host cells, through the spike (S) protein that exists on its surface. This binding causes the entry of the virus into cells of the host organism. The actual mechanism used by the COVID-19 virus to induce disease is still speculative. A total of 44,322,504 cases, a 1,173,189 death toll and 32,486,703 recovery cases have been reported in 217 countries globally as of 28 October 2020. Symptoms from the infection of the virus include chest pain, fever, fatigue, nausea, and others. Acute respiratory stress syndrome, arrhythmia, and shock are some of the chronic manifestations recorded in severe COVID-19. Transmission is majorly by individual-to-individual through coughing, sneezing, etc. The lack of knowledge regarding the mechanism of and immune response to the virus has posed a challenge in the development of a novel drug and vaccine. Currently, treatment of the disease involves the use of anti-viral medications such as lopinavir, remdesivir, and other drugs. These drugs show some efficacy in the management of COVID-19. Studies are still on-going for the development of an ideal and novel drug for treatment. In terms of natural product intervention, Traditional Chinese Medicines (TCM) have been employed to alleviate the clinical manifestation and severity of the disease and have shown some efficacy. This review presents an updated detailed overview of COVID-19 and the virus, concerning its structure, epidemiology, symptoms and transmission, immune responses, and current interventions, and highlights the potential of TCM. It is anticipated that this review will further add to the understanding of COVID-19 and the virus, hence opening new research perspectives.