Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutated receptor binding domain with ACE2 receptor

Dash, Pujarini; Turuk, Jyotirmayee; Behera, Santosh Ku; Palo, Subrata Kumar; Raghav, Sunil K.; Ghosh, Arup; Sabat, Jyotsnamayee; Rath, Sonalika; Subhadra, Subhra; Rana, Khokan; Bhattacharya, Debdutta; Kanungo, Srikanta; Kshatri, Jaya Singh; Mishra, Bijaya Kumar; Dash, Saroj; Parida, Ajay; Pati, Sanghamitra

OBJECTIVE: SARS-CoV-2 has affected the whole world including Odisha, a state in eastern India. Many people migrated in the state from different countries as well as states during this SARS-CoV-2 pandemic. The aim of this study was to analyze the RNA binding domain (RBD) sequence of spike protein from the isolates collected from the throat swab samples of COVID-19 positive cases and further to assess the RBD affinity with ACE2 of different species including human. METHODS: Whole genome sequencing for 35 clinical SARS-CoV-2 isolates from COVID-19 positive patients was performed using ARTIC amplicon based sequencing. Sequence analysis and phylogenetic analysis was carried out for the Spike and RBD region of all isolates. The interaction between the RBD and ACE2 receptor of five different species was also analysed. RESULTS: Spike region of 32 isolates showed one/multiple alterations in nucleotide bases in comparison to the Wuhan reference strain. One of the identified mutation at 1204 (Ref A, RMRC 22 C) in the RBD of spike protein showed a stronger binding affinity with human ACE2 receptor. Furthermore, RBDs of all the Indian isolates showed binding affinity for ACE2 of different species. CONCLUSION: As mutated RBD showed stronger interaction with human ACE2, it could potentially result in higher infectivity. Binding affinity of RBDs for ACE2 of all the five species studied, suggests that the virus can infect a wide variety of animals which could also act as natural reservoir for SARS-CoV-2.