Genome-wide identification and prediction of SARS-CoV-2 mutations show an abundance of variants: Integrated study of bioinformatics and deep neural learning.

Genomic data analysis is a fundamental system for monitoring pathogen evolution and the outbreak of infectious diseases. Based on bioinformatics and deep learning, this study was designed to identify the genomic variability of SARS-CoV-2 worldwide and predict the impending mutation rate. Analysis of 259044 SARS-CoV-2 isolates identified 3334545 mutations with an average of 14.01 mutations per isolate. Globally, single nucleotide polymorphism (SNP) is the most prevalent mutational event. The prevalence of C > T (52.67%) was noticed as a major alteration across the world followed by the G > T (14.59%) and A > G (11.13%). Strains from India showed the highest number of mutations (48) followed by Scotland, USA, Netherlands, Norway, and France having up to 36 mutations. D416G, F106F, P314L, UTR:C241T, L93L, A222V, A199A, V30L, and A220V mutations were found as the most frequent mutations. D1118H, S194L, R262H, M809L, P314L, A8D, S220G, A890D, G1433C, T1456I, R233C, F263S, L111K, A54T, A74V, L183A, A316T, V212F, L46C, V48G, Q57H, W131R, G172V, Q185H, and Y206S missense mutations were found to largely decrease the structural stability of the corresponding proteins. Conversely, D3L, L5F, and S97I were found to largely increase the structural stability of the corresponding proteins. Multi-nucleotide mutations GGG > AAC, CC > TT, TG > CA, and AT > TA have come up in our analysis which are in the top 20 mutational cohort. Future mutation rate analysis predicts a 17%, 7%, and 3% increment of C > T, A > G, and A > T, respectively in the future. Conversely, 7%, 7%, and 6% decrement is estimated for T > C, G > A, and G > T mutations, respectively. T > G\A, C > G\A, and A > T\C are not anticipated in the future. Since SARS-CoV-2 is mutating continuously, our findings will facilitate the tracking of mutations and help to map the progression of the COVID-19 intensity worldwide.

Prediction of the Effects of Variants and Differential Expression of Key Host Genes ACE2, TMPRSS2, and FURIN in SARS-CoV-2 Pathogenesis: An In Silico Approach.

A new strain of the beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is solely responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although several studies suggest that the spike protein of this virus interacts with the cell surface receptor, angiotensin-converting enzyme 2 (ACE2), and is subsequently cleaved by TMPRSS2 and FURIN to enter into the host cell, conclusive insight about the interaction pattern of the variants of these proteins is still lacking. Thus, in this study, we analyzed the functional conjugation among the spike protein, ACE2, TMPRSS2, and FURIN in viral pathogenesis as well as the effects of the mutations of the proteins through the implementation of several bioinformatics approaches. Analysis of the intermolecular interactions revealed that T27A (ACE2), G476S (receptor-binding domain [RBD] of the spike protein), C297T (TMPRSS2), and P812S (cleavage site for TMPRSS2) coding variants may render resistance in viral infection, whereas Q493L (RBD), S477I (RBD), P681R (cleavage site for FURIN), and P683W (cleavage site for FURIN) may lead to increase viral infection. Genotype-specific expression analysis predicted several genetic variants of ACE2 (rs2158082, rs2106806, rs4830971, and rs4830972), TMPRSS2 (rs458213, rs468444, rs4290734, and rs6517666), and FURIN (rs78164913 and rs79742014) that significantly alter their normal expression which might affect the viral spread. Furthermore, we also found that ACE2, TMPRSS2, and FURIN proteins are functionally co-related with each other, and several genes are highly co-expressed with them, which might be involved in viral pathogenesis. This study will thus help in future genomics and proteomics studies of SARS-CoV-2 and will provide an opportunity to understand the underlying molecular mechanism during SARS-CoV-2 pathogenesis.

First detection of SARS-CoV-2 genetic material in the vicinity of COVID-19 isolation Centre in Bangladesh: Variation along the sewer network.

We made the first and successful attempt to detect SARS-CoV-2 genetic material in the vicinity wastewaters of an isolation centre i.e. Shaheed Bhulu Stadium, situated at Noakhali, Southeastern Bangladesh. Owing to the fact that isolation centre, in general, always contained a constant number of 200 COVID-19 patients, the prime objective of the study was to check if several drains carrying RNA of coronavirus are actually getting diluted or accumulated along with the sewage network. Our finding suggested that while the temporal variation of the genetic load decreased in small drains over the span of 50 days, the main sewer exhibited accumulation of SARS-CoV-2 RNA. Other interesting finding displays that probably distance of sampling location in meters is not likely to have a significant impact on the detected gene concentration, although the quantity of the RNA extracted in the downstream of the drain was higher. These findings are of immense value from the perspective of wastewater surveillance of COVID-19, as they largely imply that we do not need to monitor every wastewater system, and probably major drains monitoring may illustrate the city health. Perhaps, we are reporting the accumulation of SARS-CoV-2 genetic material along with the sewer network i.e. from primary to tertiary drains. The study sought further data collection in this line to simulate conditions prevailed in most of the developing countries and to shed further light on decay/accumulation processes of the genetic load of the SARS-COV-2.