Medical Sciences

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Objective: The main objective of this CSIR-NMITLI project is to generate a panel of human monoclonal antibodies (hmAbs) against the viral RBD protein that can neutralize the SARS CoV-2 virus. The specific objectives are: Generation of human monoclonal antibodies (hmAbs) to SARS-Cov-2 from convalescent phase of COVID-19 patients. Characterization of isolated hmAbs: selection of high affinity and neutralizing antibodies Probing virus-receptor interactions to anticipate future adaptation strategies that could be employed by SARS-CoV-2.

Summary: The recurrence of epidemics due to newly emerging strains of CoV is a cause of concern as it highlights the continual threat posed to human health by this family of viruses. As an RNA virus, the intrinsically high mutation rates coupled with facile capacity for inter-species transmission probably explains why corona viruses are the main cause of emerging diseases today. Importantly, these traits underscore the need to also look beyond the immediate concern of controlling the current pandemic, and remain alert for virus variants with increased pathogenicity, and/or with an acquired capability for immune escape. Further, the likelihood of such variants arising out of intra-population variation during the current epidemic can also not be ignored. Comparative analysis suggests that the S1-RBD protein of SARS-CoV2 evolves at a quickened pace. This feature may be associated with its location on the very top of the prefusiontrimeric spike, which is the most protruding and exposed area on virions. As a result, S1-RBDs are under heavy selective pressure to escape host immune surveillance. Therefore, given that studies so far suggest that immunity to SARS-CoV2 infection depends on antibodies targeting the S1-RBD, the vulnerability of this domain to undergo antigenic drift over time is a matter of concern. Such a drift could potentially lead to either immune escape, or even increased virulence due to receptor switching. Thus, the project targets the following unmet and urgent need to combat the global pandemic: Generation of hmAbs against SARS-CoV2 for the immediate deployment for the treatment of the infected. Mapping the trajectory of the mutations in RBD domain of S1 protein to anticipate future adaptation of the virus Generation of hmAbs clones that can bind to the mutated RBD protein, that could be readily used for combating future SARS-CoV infections. The project is being implemented by two institutional partners, NCCS Pune and IIT Indore while the participating industry partners are BBIL, Hyderabad and Predomix Technologies, Gurugram at a cost of Rs 140.80 lakh for one year.

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