Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of this century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to genetic pool of the local populations.
Methods: For this study, we have analysed 1,921 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL pro ) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements.
Results: Our results demonstrate that bat-CoV shares >96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. The study further investigated the interaction of repurposed drugs with SARS-CoV-2 3CL pro enzyme which regulates viral replication machinery, using state of the art in silico approaches.
Conclusions: Overall, this study provides insights into the evolving mutations with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat Covid-19 pandemic.