Abstract
The mortality rates due to COVID-19 have been found disproportionate globally and are currently being researched. India mortality rate with a population of 1.3 billion people is relatively lowest to other countries with high infection rates. Genetic composition of circulating isolates continues to be a key determinant of virulence and pathogenesis. This study aimed to analyse the extent of divergence between genomes of Indian isolates (n = 2525 as compared to reference Wuhan-1 strain and isolates from countries showing higher fatality rates including France, Italy, Belgium, and the USA. The study also analyses the impact of key mutations on interactions with angiotensin converting enzyme 2 (ACE2) and panel of neutralizing monoclonal antibodies. Using 1,44,605 spike protein sequences, global prevalence of mutations in spike protein was observed. The study suggests that SARS-CoV-2 genomes from India share consensus with global trends with respect to D614G as most prevalent mutational event (81.66% among 2525 Indian isolates). Indian isolates did not reported prevalence of N439K mutation in receptor binding motif (RBM) as compared to global isolates (0.54%). Computational docking and molecular dynamics simulation analysis of N439K mutation with respect to ACE 2 binding and reactivity with RBM targeted antibodies viz., B38, BD23, CB6, P2B–F26 and EY6A suggests that variant have relatively higher affinity with ACE 2 receptor which may support higher infectivity. The study warrants large scale monitoring of Indian isolates as SARS-CoV-2 virus is expected to evolve and mutations may appear in unpredictable way.
Highlights
The current 2019 coronavirus pandemic (COVID-19) is caused by a positive RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]
We report here comparative genomics of Pan India isolates (n 1⁄4 2525) vis a vis reference genome and isolates from countries showing high fatality rates including France, Italy, Belgium, and the USA
To better define the receptor-binding motif (RBM)'s mutations N439K for antibody escape, we examined structural and binding constraint in the epitopes of antibodies with prototype structures of SARS-CoV-2 receptor binding domain (RBD)
Summary
The current 2019 coronavirus pandemic (COVID-19) is caused by a positive RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. Despite all the global efforts, the virus continues to spread and infect a large population and has affected 218 countries, with more than 101,053,721 confirmed cases, 2,182,867 deaths globally (WHO, 29 Jan 2021) [2]. The second most populated country, reported 7,761,312 cases in all with 117,306 deaths (WHO, October 23) [4]. Trends in mortality rates in India are intriguing, despite the second largest reported cases of infection ("https://covid19.who.int/table"), second after the USA (more than 76 lakh) in terms of total confirmed cases. Numerous hypotheses are proposed, one hypothesis includes the variability of circulating viral strains. Monitoring this variability in key viral genomes and immune-dominant antigens may explain the infectivity, pathogenesis, and transmission of SARS-CoV-2 [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
