This evidence review was compiled by members of the CITF Secretariat with the input from experts affiliated with the CITF and does not necessarily reflect the views of all CITF members.
By Mariana Bego
A recent state-of-the-art review in Nature Microbiology summarizes the latest evidence regarding the molecules in our cells that allow SARS-CoV-2 to infect us and how these may give us clues to discover new anti-viral drugs.
As intracellular parasites, viruses depend on host cell factors and machinery to grow and replicate. This review summarizes the host factors needed for SARS-CoV-2 replication cycles. The review compares SARS-CoV-2 to other viruses and highlights certain host factors that may have potential to be targeted for COVID-19 antiviral therapies.
- Besides the well-described main receptor angiotensin-converting enzyme 2 (ACE2) that SARS-CoV-2 uses to enter host cells, the virus may find other means to enter host cells such as heparan sulfate (HS), neuropilin-1 (NRP1), and scavenger receptor class B member 1 (SRB1) among others.
- After the initial binding with the host receptor protein, SARS-CoV-2 spike protein needs to be cleaved by cellular proteases.
- A number of genetic screenings identified several other host proteins required for SARS-CoV-2 replication cycles.
- Many of these host factors have existing drugs targeting them. These drugs could potentially be repurposed as antiviral therapies. Drug repurposing approaches bypass costly and time-consuming drug discovery processes and are often already proven safe and approved for use in humans. Examples of this include existing drugs that reduce the availability of the receptor ACE2, making it difficult for the virus to infiltrate the host cells.
- ‘Druggable’ host factors used by SARS-CoV-2 and potentially by other pathogenic coronaviruses could be developed as broad-spectrum antivirals to be deployed in the existing and possible future pandemics.
Baggen J, Vanstreels E, Jansen S, Daelemans D. Cellular host factors for SARS-CoV-2 infection. Nat Microbiol. 2021 Sept 01. doi: 10.1038/s41564-021-00958-0