Systematic structure guided clustering of chemical lead compounds targeting RdRp of SARS-CoV-2

BACKGROUND: To combat the global health issue caused by SARS-CoV2, scientists are attempting various therapeutic approaches towards drug discovery including computational biology and drug-repurposing. Recent studies have highlighted the conserved nature of RNA-dependent RNA polymerase (RdRp) of coronaviruses affecting human, bat and animals. In this study attempts have been made to identify the potential inhibitors of RdRp by utilizing molecular docking and MD simulation studies. METHOD(S): Systematic structure-based screening of chemical compounds from public libraries was performed to identify the potential lead molecules inhibiting RdRp. This structure driven clustering of compounds is based on decision tree model generated by combining two properties: 1) shape descriptors;and 2) critical number of multiple bonds. The enabled screening of potential chemical compounds was subjected to molecular docking followed by molecular dynamics simulation studies. RESULT(S): The results revealed that the stability of protein-drug complex structure was in the order of RdRp-Oxoglaucine >RdRp-Flutroline >RdRp-Brucine complex. CONCLUSION(S): This study identifies Oxoglaucine, Brucine and Flutroline as prospective inhibiting agents of SARS-CoV-2 RdRp and further warrants for experimental validation. Copyright © 2022 EDIZIONI MINERVA MEDICA.

In-silico analysis of multiepitope based vaccine targeting respiratory viruses SARS, MERS and SARS-CoV-2

BACKGROUND: Recurrent outbreaks of respiratory viruses like SARS-CoV (severe acute respiratory syndrome-coronavirus, 2002), MERS (Middle East respiratory syndrome, 2012) including the ongoing SARS-CoV-2 (2019) pandemic warrants for a single-broad-spectrum vaccine against these respiratory viruses. METHOD(S): In the present study, phylogenetic analysis followed by in-silico identification of vaccine candidates for SARS, MERS and SARS-CoV-2 was performed by exploiting T-cell and B-cell mapping to ascertain the best possible epitopes for effector humoral- and cell-mediated immune response. Further, population-coverage analysis of the identified epitopes followed by the designing of chimera of epitope-based vaccine was done using linkers and adjuvants. Docking study was done to appraise the interaction of the proposed vaccine with ACE2 (angiotensin converting enzyme-2) receptor (SARS and SARS-CoV-2) and HLA-B7 (human leukocyte antigen) receptor (MERS). The stability of the vaccine chimera was confirmed by molecular dynamics performed for 20 ns;this was followed by codon optimization and in-silico cloning. RESULT(S): Phylogenetic analysis revealed similarity among SARS-CoV-2, SARS-CoV and bat SARS-like coronavirus. Both, SARS-CoV and SARS-CoV-2 were from different class than MERS, whereas SARS-CoV-2 showed more relatedness with Bat SARS-like coronaviruses. The most suitable epitopes found were LSFELLNAPATVCGP (SARS), LVTLAILTALRLCAY (SARS-CoV-2) and YTSAFNWLL (MERS) with nearly 98% population coverage. Molecular docking followed by simulation studies revealed high number of hydrogen bonds, stable RMSD values and acceptable RMSF flexibility scores, indicating stable interactions of the vaccine with ACE2 and MHC receptors (Major histocompat-ibility complex). Expression of the designed multiepitope vaccine in E. coli (Escherichia coli) expression system was confirmed by in-silico cloning/codon optimization. CONCLUSION(S): Further, in-vitro and in-vivo experimental validation studies are required to endorse our current findings. Copyright © 2022 EDIZIONI MINERVA MEDICA.

A cross-sectional analysis of post-acute COVID-19 symptoms.

Objectives: The severe acute respiratory syndrome (COVID-19) due to SARS-CoV-2 was first reported in China in December 2019 and has generated a worldwide pandemic. The objective of the research is to examine and describe (a) the symptoms that persist after the end of the acute stage and (b) their relationship with the severity of the disease. Study Design: This study is a cross-sectional study conducted in the Kingdom of Bahrain on COVID-19 infected patients using an online survey questionnaire with a total number of 52 patient responses (29 females and 23 males). Method: A scale (0 no symptoms to 10 very high symptoms intensity) was assessed in patients after 3 months to detect the relevance of specific symptoms post-COVID-19 such as emotional and physical health, headache, dyspnoea, pain (muscles/joints/chest), anosmia, vertigo, neurologic symptoms, sarcopenia, delirium. Results: The most common COVID-19 symptoms were reported to be fever (69.2%), headache (59.6%), and cough (50.0%). Data analysis showed that BMI was not correlated with any post-acute COVID-19 symptoms. Regarding the post-acute COVID-19 symptoms, this study showed that an increase of intensity of headache was associated with an increase of delirium; an increase of intensity of dyspnoea was associated with an increase of pulmonary dysfunction. The increase of anosmia and dysgeusia was associated with an increase in delirium. In addition, the increase of neurological symptoms and delirium were associated with the increase of sarcopenia. The most common persistent post-COVID-19 symptoms observed in this study were emotional stress, followed by loss of smell and taste, and neurological symptoms. Conclusions: Therefore, follow-up and rehabilitation care for COVID-19 patients must be focused on addressing the needs of these people in the longer term.

COVID-19 Knowledge, Attitudes, and Preventive Measures of University Students in Bahrain.

Background: The severe, acute respiratory syndrome COVID-19 that was first reported in China in December 2019 quickly became a global pandemic that has resulted in over 100 million infections and more than 2 million deaths. Study Design: This study aimed to assess the awareness level of university students regarding the possibility of becoming infected with COVID-19. In order to achieve this objective, we assessed the students' knowledge, attitudes, and behaviors using an online survey questionnaire offered to a total of 300 students. Results: A positive response regarding awareness of COVID-19 symptoms was registered by more than 70% of the students, whereas 62% felt that wearing a mask did not give full protection against infection, approximately 30% agreed that antibiotics and antivirals did not treat COVID-19, and 62% agreed that vitamin C was helpful in treating common symptoms of COVID-19. Moreover, around 31% of the students believed that COVID-19 is a man-made virus. Students who had gotten infected with SARS-CoV-2 believed that wearing a mask gives full protection (p=0.018). In response to survey questions related to attitude, 80% of students cancelled and postponed meetings with friends, and 90% agreed that mask-wearing is the most precautionary measure used to prevent the infection. In addition, 82% avoided coughing in public, 82% avoided contact if they felt flu-like symptoms and 80% washed their hands far more often due to the pandemic. Interestingly, 76% carried hand sanitizer, 66.5% avoided shaking hands, and 42.7% were taking vitamin C supplements. Conclusions: This study showed that the participants had a positive awareness of COVID-19 transmission, symptoms, and treatments misconceptions and mistaken beliefs related to treatments and the origin of the virus were also common and should be addressed. This study thus provides a baseline for a population-based surveillance program that could help local authorities to improve pandemic preparation plans, particularly with regard to governmental education and media campaigns.

Clearing the air about airborne transmission of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has created the current pandemic, has caused a worldwide worry. Different countries have since enforced varying levels of lockdowns and guidelines for their populations to follow in a serious effort to mitigate the spread. Up until recently, the majority of these regulations and policies were established on the assumption that the dominant routes of transmission of this virus are through droplets and fomite contact. However, there is now a substantial amount of research pointing towards the strong possibility that SARS-CoV-2 can spread through airborne means. The World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) have recently recognized this, which poses the question of whether our collective methods of lessening transmission risk and keeping people safe have been sufficient. This paper is a comprehensive review of the evidence on SARS-CoV-2 being an airborne disease, through different epidemiological, experimental, and animal-model based published research. Studies opposing this evidence have also been discussed. The majority of these studies are favoring the high plausibility of SARS-CoV-2 aerosol transmission, and therefore the many implications of aerosol transmission have been discussed in this paper to suggest effective mitigation and control strategies.

Variants of SARS-CoV-2, their effects on infection, transmission and neutralization by vaccine-induced antibodies.

OBJECTIVE: The current study reviewed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) variants for their effects on infection, transmission and neutralization by vaccine-induced antibodies. MATERIALS AND METHODS: The research articles for the current study were searched over PubMed, Google Scholar, EMBASE and Web of Science online databases. The keywords used were: (("SARS-CoV-2" OR "COVID-19") AND ("mutation" OR "variant") AND ("death" OR "hospitalization" OR "infection" OR "transmission") AND ("antibody" OR "neutralize" OR "vaccine")). A total of 333 research articles were retrieved through online-database search. These articles were further scrutinized for their relevancy. Additionally, searches were performed to find the latest relevant information over Google search engine and relevant news browsers. Finally, around 35 germane articles were considered for scripting the current report. RESULTS: The mutations have changed amino acids at key positions in spike protein viz. S477N, E484K, Q677H, E484Q, L452R, K417T, K417N and N501Y. These mutations are relevant for different characteristics and are present in newly evolved strains of SARS-CoV-2 like E484K in B.1.526, B.1.525, P.2, B.1.1.7, P.1 and B.1.351. Mutations have increased the immune escape potential leading to 3.5-6.5-folds decrease in neutralization of antibodies (Pfizer and Moderna vaccines). The variant, B.1.617 circulating in India and many other countries (double variant) having E484Q and L452R mutations, has raised the infection rate and decreased the neutralization capacity of the vaccine-induced antibodies. Deadly K417N+E484K+N501Y triplet mutations found in B.1.351 and P.1 have increased the transmission ability of these strains by 50% leading to greater COVID-19 hospitalization, ICU admissions and deaths. CONCLUSIONS: The new SARS-CoV-2 variants have compromised the neutralization potential of the currently used vaccines, but still, they have considerable efficacy to reduce infection and mortality. GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract.jpg.

SARS-CoV-2 viral load as an indicator for COVID-19 patients' hospital stay

Background/objective: The novel coronavirus disease 2019 (COVID-19) pandemic has posed a global threat to public health. An objective strategy is quintessential to handle resources prudently. This study assessed the utility of the quantitative polymerase chain reaction (qPCR) cycle of threshold (Ct) to evaluate the severity of the COVID-19 infection. The study also assessed the duration of the hospital and the management of healthcare resources.