Association between TCF7L2 polymorphism and type 2 diabetes mellitus susceptibility: a case-control study among the Bangladeshi population.

BACKGROUND: Diabetes is a severe health burden for Bangladesh. Genetic polymorphism has been reported to be one of the major risk factors for diabetes in various studies. TCF7L2 (transcription factor 7 like 2) transcripts in the human ß-cell have effects on ß-cell survival, function, and Wnt signaling activation. This study aimed to evaluate the frequency and association of various polymorphisms namely TCF7L2 rs12255372 and rs7903146 among Bangladeshi patients with T2DM (Type 2 Diabetes Mellitus). METHODS: This case-control study included 300 patients with T2DM and 234 healthy individuals from two health facilities in the Chattogram Division of Bangladesh. Anthropometric measurements were assessed using a self-reported, structured, eight-item questionnaire. The polymorphisms were identified by PCR-RFLP and sequencing method. RESULTS: A strong association of T2DM with polymorphisms was observed, including rs12255372 (p = 0.0004) and rs7903146 (p = 0.005). It was observed that the risk genotype at rs12255372 was associated with age (p = 0.009), a family history of diabetes (p < 0.0001), and HbA1C (p < 0.0001). Furthermore, it was found that rs12255372 was substantially associated with hypertension (p = 0.03), eye problems (p = 0.01), and neurological abnormalities (p = 0.02). CONCLUSION: This study postulates that TCF7L2 genetic polymorphism is associated with the risk of T2DM among the studied Bangladeshi population. The findings should be replicated through more studies with a large number of samples and in different populations.

Induced dormancy in Indian meal moth Plodia interpunctella (Hübner) and its impact on the quality improvement for mass rearing in parasitoid Habrobracon hebetor (Say).

A steady supply of hosts at the susceptible stage for parasitism is a major component of mass rearing parasitoids for biological control programs. Here we describe the effects of storing 5th instar Plodia interpunctella larvae in dormancy on subsequent host development in the context of host colony maintenance and effects of the duration of host dormancy on the development of Habrobracon hebetor parasitoids reared from dormant hosts. We induced dormancy with a combination of short daylength (12L:12D) and lower temperature (15°C), conditions known to induce diapause in this species, and held 5th instar larvae of P. interpunctella for a series of dormancy durations ranging from 15 to 105 days. Extended storage of dormant 5th instar larvae had no significant impacts on survival, development, or reproductive potential of P. interpunctella, reinforcing that dormant hosts have a substantial shelf life. This ability to store hosts in dormancy for more than 3 months at a time without strong negative consequences reinforces the promise of using dormancy to maintain host colonies. The proportion of hosts parasitized by H. hebetor did not vary significantly between non-dormant host larvae and dormant host larvae stored for periods as long as 105 days. Concordant with a prior study, H. hebetor adult progeny production from dormant host larvae was higher than the number of progeny produced on non-dormant host larvae. There were no differences in size, sex ratio, or reproductive output of parasitoids reared on dormant hosts compared to non-dormant hosts stored for up to 105 days. Larval development times of H. hebetor were however longer when reared on dormant hosts compared to non-dormant hosts. Our results agree with other studies showing using dormant hosts can improve parasitoid mass rearing, and we show benefits for parasitoid rearing even after 3 months of host dormancy.

Investigating Antimicrobial Resistance and ESBL Producing Gene in Klebsiella Isolates among Neonates and Adolescents in Southern Bangladesh.

Background: Multidrug-resistant (MDR) clones of Klebsiella pneumoniae (Kpn) have been increasingly documented in community-acquired and nosocomial infections all around the globe. Extended-spectrum ß-lactamases (ESBLs) are a rapidly evolving group of ß-lactamase enzymes derived from SHV genes by mutations. This research work aimed to investigate and analyze the widespread prevalence of Kpn antibiotic resistance in different areas of the southern part of Bangladesh. Methods: This particular study was executed and implemented by using 501 clinical samples or isolates from two different hospitals in Chattogram. The disk diffusion method was used to detect Kpn's sensitivity to 16 antibiotics in a drug susceptibility test. By using the PCR technique, the widespread prevalence of antibiotic-resistant gene blaSHV-11 was studied. Sequencing along with phylogenetic analysis was utilized to verify isolates with the blaSHV-11 gene. Results: Almost all of the Kpn isolates were spotted to be antibiotic-resistant. These Kpn isolates were resistant to ß-lactams, aminoglycosides, and quinolones at high levels. The spatial analysis displayed that infections involving Kpn were more common in the urban areas (70%) than in the rural areas (30%). Neonates had substantially higher levels (p < 0.001) of resistance to multidrug than other age groups. Cefepime was identified as the most frequent antibiotic-resistant to all age groups (56.68%). The highest numbers of resistant isolates (36.92%) were found in urine samples. The ESBL gene blaSHV-11 was found in 38% isolates. Conclusion: The significant frequency of MDR Kpn harboring ß-lactamases and AMR genes strongly suggests the requirement to develop effective antimicrobial resistance control and prevention measures in Bangladesh.

Therapeutic Intervention of COVID-19 by Natural Products: A Population-Specific Survey Directed Approach.

To date very few promising leads from natural products (NP) secondary metabolites with antiviral and immunomodulatory properties have been identified for promising/potential intervention for COVID-19. Using in-silico docking studies and genome based various molecular targets, and their in vitro anti-SARS CoV-2 activities against whole cell and/or selected protein targets, we select a few compounds of interest, which can be used as potential leads to counteract effects of uncontrolled innate immune responses, in particular those related to the cytokine storm. A critical factor for prevention and treatment of SARS-CoV-2 infection relates to factors independent of viral infection or host response. They include population-related variables such as concurrent comorbidities and genetic factors critically relevant to COVID-19 health disparities. We discuss population risk factors related to SARS-CoV-2. In addition, we focus on virulence related to glucose-6-phosphate dehydrogenase deficiency (G6PDd), the most common human enzymopathy. Review of data on the response of individuals and communities with high prevalence of G6PDd to NP, prompts us to propose the rationale for a population-specific management approach to rationalize design of therapeutic interventions of SARS-CoV-2 infection, based on use of NP. This strategy may lead to personalized approaches and improve disease-related outcomes.

Effects of low temperatures on quiescence in Trichogramma evanescens Westwood and T. chilonis Ishii reared on Plodia interpunctella (Hübner): implications for mass rearing.

The egg parasitoids of the genus Trichogramma are important potential biological control agents for a wide range of lepidopteran pests. Cold storage of host eggs has been proposed as a valuable technique for ensuring the release of sufficient parasitoid numbers whenever it is needed. In this context, the impact of low temperatures to induce quiescence in T. evanescens Westwood and T. chilonis Ishii was studied using eggs of Indian meal moth Plodia interpunctella (Hübner). Prepupae of the parasitoids were stored for 15, 30, 45, 60 and 75 d at 4 °C, following a 7 d period of acclimation at 10 °C. Both parasitoid species seem to survive unfavorable temperature conditions by entering a state of quiescence. Parasitism, adult emergence, sex ratio and progeny quality were not affected by cold storage in either parasitoid species for up to 30 d of storage. Parasitized host eggs of P. interpunctella can be stored for up to 60 d at 4 °C for both parasitoids, but there was no emergence at 75 d. General productivity values gradually decreased as the duration of storage lengthened for both species. Our results clearly reveal that the eggs parasitized by these species can be stored for up to 30 d at 4 °C in a state of quiescence without much loss of their performance compared to the control eggs.

Genetic determinants of SARS-CoV-2 and the clinical outcome of COVID-19 in Southern Bangladesh.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on population health. The genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Bangladesh are not well understood. METHODS: This study aimed to determine the genomic variation in SARS-CoV-2 genomes that have evolved over 2 years of the pandemic in southern Bangladesh and their association with disease outcomes and virulence of this virus. We investigated demographic variables, disease outcomes of COVID-19 patients and genomic features of SARS-CoV-2. RESULTS: We observed that the disease severity was significantly higher in adults (85.3%) than in children (14.7%), because the expression of angiotensin-converting enzyme-2 (ACE-2) diminishes with ageing that causes differences in innate and adaptive immunity. The clade GK (n = 66) was remarkable between June 2021 and January 2022. Because of the mutation burden, another clade, GRA started a newly separated clustering in December 2021. The burden was significantly higher in GRA (1.5-fold) highlighted in mild symptoms of COVID-19 patients than in other clades (GH, GK, and GR). Mutations were accumulated mainly in S (22.15 mutations per segment) and ORF1ab segments. Missense (67.5%) and synonymous (18.31%) mutations were highly noticed in adult patients with mild cases rather than severe cases, especially in ORF1ab segments. Moreover, we observed many unique mutations in S protein in mild cases compared to severe, and homology modeling revealed that those might cause more folding in the protein's alpha helix and beta sheets. CONCLUSION: Our study identifies some risk factors such as age comorbidities (diabetes, hypertension, and renal disease) that are associated with severe COVID-19, providing valuable insight regarding prioritizing vaccination for high-risk individuals and allocating health care and resources. The findings of this work outlined the knowledge and mutational basis of SARS-CoV-2 for the next treatment steps. Further studies are needed to confirm the effects of structural and functional proteins of SARS-CoV-2 in detail for monitoring the emergence of new variants in future.

Improved Quality Management of the Indian Meal Moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae) for Enhanced Efficacy of the Sterile Insect Technique.

The sterile insect technique (SIT) is considered an environmentally friendly, autocidal control tactic to manage insect pests. This work dealt with the improvement of quality management of the Indian meal moth Plodia interpunctella (Hübner) for enhanced efficacy of the SIT. The results indicated that egg hatching of irradiated mature eggs of P. interpunctella was higher than that of younger eggs, indicating that mature eggs were significantly more tolerant than younger eggs. Moreover, our data revealed that a dose of 500 Gy completely prevented pupal formation in irradiated young and mature larvae. Crosses between irradiated and non-irradiated adults resulted in considerable variations in fecundity. The mating competitiveness index (CI) value was higher for a ratio of 5:1:1 (sterile male, fertile male, and fertile female, respectively) as compared with the ratio 1:1:1 for the irradiated individuals of all life stages. Low temperature (5 °C) maintenance of irradiated pupae significantly affected adult emergence. Using cylinders to assess flight ability, we found that the flight performance of adults that were developed from cold treated irradiated pupae was influenced by cylinder diameter, cylinder height and the number of hours the insects were in the cylinders. The percentage of DNA damage of the reproductive organs of adults developed from cold treated pupae that were irradiated with 100 and 150 Gy varied significantly. The results of this study should be used to implement pilot-scale field tests aiming at a sterile- to-fertile male ratio of 5 to 1.

Knowledge and attitudes of thalassaemia among high-risk indigenous university students in Bangladesh: A pilot study.

BACKGROUND AND OBJECTIVES: Thalassaemia is an inherited life-threatening but preventable haemoglobin disorder. South Asian countries, including Bangladesh, are the hotspots of the world's thalassaemia belt. Indigenous communities are underprivileged and vulnerable to genetic disorders, including thalassaemia. Understanding the perspectives of thalassaemia of future community leaders (indigenous university students) is critical for developing a tailor-made preventive strategy relevant to their communities. In this study, we aimed to assess the level of knowledge and attitudes towards thalassaemia among indigenous university students and determine their thalassaemia carrier status. METHODS: A cross-sectional survey was conducted among 251 tribal university students using a published questionnaire between May and October 2018. The main survey instrument consisted of 22 anonymous questions. Descriptive and inferential statistical procedures were used for data analysis. RESULTS: More than half (55%) of the indigenous students had never heard the term 'thalassaemia'. Around half (49%) of the marriages in their communities were consanguineous. The mean knowledge score was abysmal (4.91±2.65 out of a 12-point scale), which was not associated with the consanguinity of their parent but home districts. Multiple linear regression of demographic variables on the total knowledge score revealed that the overall knowledge is significantly associated with their home district (p< 0.05). Participants from science disciplines scored more than 1 point than their counterparts from Arts and Humanities (p = 0.08615). CONCLUSIONS: For the first time, this study has identified knowledge gaps and misperceptions about thalassaemia among university students from indigenous communities in the southeastern region of Bangladesh. This study serves as a baseline for future interventions (premarital and prenatal screening) targeting future community leaders.

Age- and time interval-specific gamma radiation-induced DNA damage in adult maize weevils, Sitophilus zeamais Motschulsky, assessed using comet assays.

The gamma radiation-induced DNA damage in adult maize weevils, Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), was assessed using single-cell electrophoresis (comet assay). Analysis of DNA damage following 0.5 and 1.0 kGy of gamma radiation was performed using cells from 1- and 15-day-old adults. Gamma-irradiated adults from both age groups showed typical DNA fragmentation, whereas cells from non-irradiated adults showed more intact DNA than young S. zeamais. Investigations using the comet assay showed that tail length, % tail DNA and % DNA damage all increased in adults of both age groups when compared to the control insects. A maximum comet length of 227.33 µm was recorded for 15-day-old adults at 24h after irradiation with 1.0 kGy and a minimum of 50.12 µm for 1-day-old adults at 0 h after irradiation with 0.5 kGy. The percentage of DNA damage increased up to 57.31% and 68.15% for 1- and 15-day-old adults, respectively, at 24h after irradiation with 1.0 kGy, whereas only 8.58% and 12.22% DNA damage were observed in the control batches. The results also showed that percentage of DNA damage increased at 24h after irradiation compared to that at 0 h. However, further studies are needed to confirm these results.

Estimating long-term spatial distribution of Plodia interpunctella in various food facilities at Rajshahi Municipality, Bangladesh, through pheromone-baited traps.

The Indian meal moth, Plodia interpunctella (Hübner), feeds on a wide range of commodities in most regions of the world. The present study presents six years of monitoring data for P. interpunctella in pheromone-baited traps by analyzing the trends of spatial variability, in five food facilities located in the Rajshahi municipality area of Bangladesh. We also tracked insect incidence at different spatial scales and evaluated the impact of food facility types and storage structures on insect populations. Our model showed an aggregated distribution pattern for P. interpunctella. Population patterns of P. interpunctella varied significantly among facilities. The highest number of moths captured was recorded in a grain retailer located at Municipal market, followed by a grain warehouse at Harian, pulse mill at Kazla, flour mill at Sapura and grocery shop at Katakhali. The population fluctuation of P. interpunctella moths was similar among the different locations tested, while there were no captures during the winter period. Our results indicate that long-term monitoring in a wide range of areas can be used to indicate population outbursts, under an area-wide management strategy.

Factors influencing the choice of monoclonal antibodies for antibody-drug conjugates.

In antibody-drug conjugates (ADCs), monoclonal antibodies (mAbs) act as carriers for a cytotoxic payload providing the therapy with targeted action against cells expressing a target cell surface antigen. An appropriate choice of mAb is crucial to developing a successful ADC for clinical development. However, problems such as immunogenicity, poor pharmacokinetic (PK) and pharmacodynamic (PD) profiles and variable drug-antibody ratios (DARs) plague ADCs. In this review, we detail recent mAb-based innovations and factors that should be considered to overcome these problems to achieve a new generation of more effective ADC therapeutics.

Effects of Diet and Temperature on the Life History of the Redlegged Ham Beetle (Coleoptera: Cleridae).

We investigated the effects of various foods and different rearing temperatures on the survival and development of the redlegged ham beetle Necrobia rufipes (De Geer) (Coleoptera: Cleridae), a serious pest of dry-cured hams. The diets tested were dried pet food, finely shredded copra, shredded cheese, dry-cured ham, ground fish meal, and mature larvae of Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). As indicated by the growth index and k-values, N. rufipes populations grew fastest on the pet food and slowest on the copra. On the other hand, N. rufipes fed both ham and T. castaneum larvae produced significantly heavier larvae. The adult beetles lived significantly longer on cheese compared to other foods. Studies conducted to determine the developmental rates of N. rufipes fed pet food at temperatures of 22, 25, 28, and 31°C showed that the total developmental time and longevity of N. rufipes significantly varied at different temperatures tested. The shortest developmental time (93.32 d) was observed at 28°C. Oviposition rate was highest for females reared at 25°C while lowest at 22°C. Based on the development, reproduction, and thermal requirements, the most suitable temperature for N. rufipes was between 28 and 31°C. The results also revealed that larval cannibalism prevailed among adult beetles.

The relationship between medical comorbidities and health-related quality of life among adults with type 2 diabetes: The experience of different hospitals in southern Bangladesh.

OBJECTIVE: Health-related quality of life (HRQoL) is a critical determinant to assess the severity of chronic diseases like diabetes mellitus. It has a close association with complications, comorbidities, and medical aid. This study aimed to estimate the prevalence of medical comorbidities and determine the relationship between comorbidities and HRQoL among type 2 diabetic patients of southern Bangladesh. METHOD: This study was a cross-sectional study conducted through face to face interviews using a pre-tested structured questionnaire and by reviewing patient's health records with prior written consent. The study was conducted on 2,136 patients with type 2 diabetes attending five hospitals of Chattogram, Bangladesh, during the tenure of November 2018 to July 2019. Quality of life was measured using the widely-used index of EQ-5D that considers 243 different health states and uses a scale in which 0 indicates a health state equivalent to death and 1 indicates perfect health status. The five dimensions of the quality index included mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. RESULTS: Patients with three comorbidities and with four or more comorbidities had a higher probability of reporting "extreme problem" or "some problem" in all five dimensions of the EQ-5D index compared with those without comorbidity (Odds ratio: mobility, 3.99 [2.72-5.87], 6.22 [3.80-10.19]; usual activity, 2.67 [1.76-4.06], 5.43 [3.28-8.98]; self-care, 2.60 [1.65-4.10], 3.95 [2.33-6.69]; pain or discomfort, 2.22 [1.48-3.33], 3.44 [1.83-6.45]; anxiety or depression, 1.75 [1.07-2.88], 2.45 [1.19-5.04]). The number of comorbidities had a negative impact on quality of life. CONCLUSION: Prevalent comorbidities were found to be the significant underlying cause of declined HRQoL. To raise diabetes awareness and for better disease management, the exposition of comorbidities in regards to HRQoL of people with diabetes should be considered for type 2 diabetes management schemas.

Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.

Pyrrolobenzodiazepines (PBDs) are naturally occurring DNA binding compounds that possess anti-tumor and anti-bacterial activity. Chemical modifications of PBDs can result in improved DNA binding, sequence specificity and enhanced efficacy. More recently, synthetic PBD monomers have shown promise as payloads for antibody drug conjugates and anti-bacterial agents. The precise mechanism of action of these PBD monomers and their role in causing DNA damage remains to be elucidated. Here we characterized the damage-inducing potential of two C8-linked PBD bi-aryl monomers in Caulobacter crescentus and investigated the strategies employed by cells to repair the same. We show that these compounds cause DNA damage and efficiently kill bacteria, in a manner comparable to the extensively used DNA cross-linking agent mitomycin-C (MMC). However, in stark contrast to MMC which employs a mutagenic lesion tolerance pathway, we implicate essential functions for error-free mechanisms in repairing PBD monomer-mediated damage. We find that survival is severely compromised in cells lacking nucleotide excision repair and to a lesser extent, in cells with impaired recombination-based repair. Loss of nucleotide excision repair leads to significant increase in double-strand breaks, underscoring the critical role of this pathway in mediating repair of PBD-induced DNA lesions. Together, our study provides comprehensive insights into how mono-alkylating DNA-targeting therapeutic compounds like PBD monomers challenge cell growth, and identifies the specific mechanisms employed by the cell to counter the same.

Prevalence and molecular characterization of antibiotic resistance and associated genes in Klebsiella pneumoniae isolates: A clinical observational study in different hospitals in Chattogram, Bangladesh.

OBJECTIVE: This study was performed to investigate the prevalence of multidrug resistance and molecular characterization of Klebsiella pneumoniae (KPN) from clinical isolates in the southern region of Bangladesh. Additional analysis of the prevalence of blaNDM-1, blaSHV-11, uge genes of KPN was also carried out among these clinical isolates. METHOD: The study was carried out using 1000 clinical isolates collected from two different hospitals of Chattogram. A drug susceptibility test was performed by the disk diffusion method to detect KPN's response to 16 antibiotics. The presence of antibiotic-resistant and (or) virulent genes blaNDM-1, blaSHV-11, uge were investigated using the PCR technique. Isolates having blaNDM-1, blaSHV-11, uge gene were further validated by sequencing followed by phylogenetic analysis. Phylogenetic relationships among these isolates were determined by Clustal omega and MEGA7. RESULT: A total of 79%, 77%, 74.9%, 71%, 66% and 65% isolates exhibited resistance against cefuroxime, cefixime, cefotaxime, ceftazidime, cefepime and ceftriaxone respectively. The frequency of resistance to other antibiotics varied from 26.5% to 61.8%. PCR analysis showed that 64% of strains harbored blaNDM-1 gene, and 38% strains harbored blaSHV-11 gene. Moreover, 47% of samples were carrying uge gene, and 19% of samples carried blaNDM-1, blaSHV-11, uge genes together. CONCLUSION: In this study, we've analysed the pattern of expression as well as prevalence of blaNDM-1, blaSHV-11, and uge genes in Klebsiella isolates. Upon molecular and statistical analysis, we found a high prevalence of multi-drug resistance KPN strains in the isolates. The Klebsiella isolates were confirmed to harbor multiple ESBL genes and 64% of the isolates were found to be producing NDM-1. As multidrug resistance is an alarming issue, continuous surveillance and routine clinical detection of resistant bacteria and plasmids are necessary to prevent catastrophic public health incidents.

Insights into the first seven-months of COVID-19 pandemic in Bangladesh: lessons learned from a high-risk country.

South Asian countries have been struggling to control the COVID-19 pandemic despite imposing months of lockdown and other public health measures. This review aims to describe the epidemiological features and shortcomings in public health preparedness to tackle COVID-19 as well as derive lessons from these events in the context of Bangladesh. We have shown that an increase in human mobility was evident throughout the lockdown period. Over 20,000 frontline health workers were affected, and more than 2100 unofficial deaths possibly linked with COVID-19 diagnosis were reported. Males were disproportionately affected in terms of infection (71%) and death (77%) than females. Over 50% of infected cases were reported among young adults (20-40-year age group). After seven months into the pandemic, a downward trend in laboratory test positive percentage was seen, although the number of new deaths per day remained largely unchanged. We believe our findings, observations and recommendations will remain as a valuable resource to facilitate better public health practice and policy for managing current and future infectious disease like COVID-19 in resource-poor developing countries.

Factors associated with low adherence to medication among patients with type 2 diabetes at different healthcare facilities in southern Bangladesh.

Background: Diabetic individuals must adhere to their medications to control their glucose levels and prevent diabetes-related complications. However, there is limited evidence of medication adherence in patients with type 2 diabetes in Bangladesh. Objectives: We assessed the level of adherence and factors associated with low adherence to anti-diabetic medication among patients with type 2 diabetes at different health facilities in southern Bangladesh. Methods: This cross-sectional study included 2,070 patients with type 2 diabetes who presented at five health facilities in the Chittagong Division between November 2018 and June 2019. We assessed medication adherence using a self-reported, structured, eight-item questionnaire and performed multiple logistic regression to investigate the factors associated with low medication adherence. Results: The overall prevalence of low medication adherence was 46.3% (95% CI: 41.4-55.8%) of our study population. Multiple logistic regression analysis revealed that males (OR: 1.37; 95% CI: 1.13-1.67), those with a family income of < 233 USD (OR: 1.54, 95% CI: 1.17-2.03), and those with a diabetic ulcer (OR: 1.42, 95% CI: 1.04-1.94) showed low adherence. Diabetic ulcers, retinopathy, and obesity were relatively more elevated among diabetic patients with low medication adherence. Conclusion: Low medication adherence among patients with type 2 diabetes in southern Bangladesh is a key public health challenge. Factors such as male sex, low annual family income, and diabetic ulcers were associated with low medication adherence. Patient counseling and awareness programs may enhance medication adherence among people with type 2 diabetes. Our findings will help physicians and public health workers to develop targeted strategies to increase awareness of the same among their patients.

Major Insights in Dynamics of Host Response to SARS-CoV-2: Impacts and Challenges.

The coronavirus disease 2019 (COVID-19), a pandemic declared by the World Health Organization on March 11, 2020, is caused by the infection of highly transmissible species of a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of July 25, 2021, there are 194,372,584 cases and 4,167,937 deaths with high variability in clinical manifestations, disease burden, and post-disease complications among different people around the globe. Overall, COVID-19 is manifested as mild to moderate in almost 90% of the cases and only the rest 10% of the cases need hospitalization. However, patients with older age and those having different comorbidities have made worst the pandemic scenario. The variability of pathological consequences and clinical manifestations of COVID-19 is associated with differential host-SARS-CoV-2 interactions, which are influenced by the factors that originated from the SARS-CoV-2 and the host. These factors usually include the genomic attributes and virulent factors of the SARS-CoV-2, the burden of coinfection with other viruses and bacteria, age and gender of the individuals, different comorbidities, immune suppressions/deficiency, genotypes of major histocompatibility complex, and blood group antigens and antibodies. We herein retrieved and reviewed literatures from PubMed, Scopus, and Google relevant to clinical complications and pathogenesis of COVID-19 among people of different age, sex, and geographical locations; genomic characteristics of SARS-CoV-2 including its variants, host response under different variables, and comorbidities to summarize the dynamics of the host response to SARS-CoV-2 infection; and host response toward approved vaccines and treatment strategies against COVID-19. After reviewing a large number of published articles covering different aspects of host response to SARS-CoV-2, it is clear that one aspect from one region is not working with the scenario same to others, as studies have been done separately with a very small number of cases from a particular area/region of a country. Importantly, to combat such a pandemic as COVID-19, a conclusive understanding of the disease dynamics is required. This review emphasizes on the identification of the factors influencing the dynamics of host responses to SARS-CoV-2 and offers a future perspective to explore the molecular insights of COVID-19.

Current Trends and Future Approaches in Small-Molecule Therapeutics for COVID-19.

The novel coronavirus (SARS-CoV-2) pandemic has created a global public health emergency. The pandemic is causing substantial morbidity, mortality and significant economic loss. Currently, no approved treatments for COVID-19 are available, and it is likely to takes at least 12-18 months to develop a new vaccine. Therefore, there is an urgent need to find new therapeutics that can be progressed to clinical development as soon as possible. Repurposing regulatory agency-approved drugs and experimental drugs with known safety profiles can provide important repositories of compounds that can be fast-tracked to clinical development. Globally, over 500 clinical trials involving repurposed drugs have been registered, and over 150 have been initiated, including some backed by the World Health Organisation (WHO). This review is intended as a guide to research into small-molecule therapies to treat COVID-19; it discusses the SARS-CoV-2 infection cycle and identifies promising viral therapeutic targets, reports on a number of promising pre-approved small-molecule drugs with reference to over 150 clinical trials worldwide, and offers a perspective on the future of the field.

Global and local mutations in Bangladeshi SARS-CoV-2 genomes.

Coronavirus Disease 2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations, and pathogenesis. Nearly 0.4 million mutations have been identified so far among the ∼60,000 SARS-CoV-2 genomic sequences. In this study, we compared a total of 371 SARS-CoV-2 published whole genomes reported from different parts of Bangladesh with 467 sequences reported globally to understand the origin of viruses, possible patterns of mutations, and availability of unique mutations. Phylogenetic analyses indicated that SARS-CoV-2 viruses might have transmitted through infected travelers from European countries, and the GR clade was found as predominant in Bangladesh. Our analyses revealed 4604 mutations at the RNA level including 2862 missense mutations, 1192 synonymous mutations, 25 insertions and deletions and 525 other types of mutation. In line with the global trend, D614G mutation in spike glycoprotein was predominantly high (98 %) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab, S, ORF3a, M, and N were significantly higher (p < 0.001) for sequences containing the G614 variant compared to those having D614. Previously reported frequent mutations, such as R203K, D614G, G204R, P4715L and I300F at protein levels were also prevalent in Bangladeshi isolates. Additionally, 34 unique amino acid changes were revealed and categorized as originating from different cities. These analyses may increase our understanding of variations in SARS-CoV-2 virus genomes, circulating in Bangladesh and elsewhere.