Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility

Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal andoropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2aclade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were alsodetected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz.G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutationsreside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain,which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observedbetween these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations ofmiRNA binding and structure were also predicted for these mutations. More importantly, the possibleimplications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of Sprotein have also been discussed. Results report for the first time a bird’s eye view on the accumulation ofmutations in SARS-CoV-2 genome in Eastern India.

Enhanced functional and structural domain assignments using remote similarity detection procedures for proteins encoded in the genome of Mycobacterium tuberculosis H37Rv.

The sequencing of the Mycobacterium tuberculosis (MTB) H37Rv genome has facilitated deeper insights into the biology of MTB, yet the functions of many MTB proteins are unknown. We have used sensitive profile-based search procedures to assign functional and structural domains to infer functions of gene products encoded in MTB. These domain assignments have been made using a compendium of sequence and structural domain families. Functions are predicted for 78 % of the encoded gene products. For 69 % of these, functions can be inferred by domain assignments. The functions for the rest are deduced from their homology to proteins of known function. Superfamily relationships between families of unknown and known structures have increased structural information by approximately 11%. Remote similarity detection methods have enabled domain assignments for 1325 'hypothetical proteins'. The most populated families in MTB are involved in lipid metabolism, entry and survival of the bacillus in host. Interestingly, for 353 proteins, which we refer to as MTB-specific, no homologues have been identified. Numerous, previously unannotated, hypothetical proteins have been assigned domains and some of these could perhaps be the possible chemotherapeutic targets. MTB-specific proteins might include factors responsible for virulence. Importantly, these assignments could be valuable for experimental endeavors. The detailed results are publicly available at http://hodgkin.mbu.iisc.ernet.in/~dots.