How SARS-Cov-2 enters in the host cell?

The recent pandemic explosion of the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), firstly originated in the Hubei province of China and subsequently spread all over the word, reached officially over three million detected cases and caused the death of more than two hundred thousand people. Scientists have begun a race toward the understanding of the mechanisms at the basis of SARS-CoV-2 viral cycle and unique features. This virus belongs to the betacoronavirus genus, together with SARS-CoV-1 and Middle East respiratory syndrome (MERS-CoV), which caused outbreaks in the last two decades.

Researches across the globe are leading to the discovery of pivotal characteristics of SARS-Cov-2, some of which shared with its ‘cousins’ SARS-Cov-1 and MERS. One of these achievements is the documentation of the mechanism of entrance into the host cell. This involves the interaction between the transmembrane viral spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell surface. The spike is a homotrimeric glycoprotein complex, in which each monomer is composed by two subunits. The S1 subunit comprises the receptor binding motif (RBM) and is responsible for the first attachment to the host receptor, while the S2 subunit mediates the membrane fusion, and requires a proteolytic cleavage executed by the host transmembrane serine protease 2 (TMPRSS2). Exciting biochemical and structural analysis of the virus-host interacting surfaces, revealed a very high binding affinity of these proteins and the occurrence of conformational changes in the complex which allow the entry of the virus. The interaction of the spike with its receptor is a key step in virus infection, which can be explained as the intimate relation of a key and its lock opening the doors to the intracellular environment. 

Advanced knowledge on the interaction between the virus and the target cells is extremely valuable and has been object of innovative studies aiming to develop vaccines and antiviral drugs, which could potentially be beneficial in our long-lasting fight against coronavirus, endowing us with potent tools and advantage in the battlefield.  

Written by Dr. Vincenzo Ruscica, Marie Sklodowska-Curie fellow

References:

  • Hoffmann et al., 2020, Cell 181, 271-280 April 16, 2020
  • Walls et al., 2020, Cell 181, 281-292, April 16, 2020
  • Shang et al., 2020, Nature, March 30, 2020
  • Lan et al., 2020, Nature, March 30, 2020