Page 73 - Covid 2021 June 2021

Analysis of the Indian SARS-CoV-2 genomes will continue as more sequences are available. The team will start sequencing of SARS-CoV-2 viruses made available and look forward to finding India-specific genetic variation. The team will also monitor the dynamics of different viral strains over time in India. Efforts are also in progress to find the functional impact of high occurrence non-synonymous mutations on the viral protein functions and use this information towards understanding immune escape mechanism and also developing mutant specific therapies.
Contact Info: skumar1@iisc.ac.in
Website link:
https://covid19.iisc.ac.in/functional-genomics-of-indian-sars-cov-2/
Targeting TMPRSS2 and Cathepsin B/L together may be synergistic
against SARS-CoV-2 infection
The entry of SARS-CoV-2 into target cells requires the activation of its surface spike protein, S, by host proteases. The host serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate S, making two independent entry pathways accessible to SARS-CoV-2. Blocking the proteases prevents SARS-CoV-2 entry in vitro. This blockade may be achieved in vivo through ‘repurposing’ existing drugs and offers a potential treatment option for COVID-19, currently in clinical trials. The researchers at Indian Institute of Science, Bangalore found that surprisingly drugs targeting the two pathways, although independent, could display strong synergy in blocking virus entry. They predicted this synergy first using a mathematical model of SARS-CoV-2 entry and dynamics in vitro. The model considered the two pathways explicitly, let the entry efficiency through a pathway depend on the corresponding protease expression level, which varied across cells, and let inhibitors compromise the efficiency in a dose-dependent manner. Analysing their model, the researchers showed that the synergy was novel and arose from effects of the drugs at both the single cell and the cell population levels. Validating our predictions, they found that available in vitro data on SARS-CoV-2 and SARS CoV entry displayed this synergy. Exploiting the synergy may improve the deployability of drug combinations targeting host proteases required for SARS-CoV-2 entry.
Contact Info: narendra@iisc.ac.in
VIGYAN PRASAR 70