Analysis of the SARS-CoV-2-host protein interaction network reveals new biology and drug candidates: focus on the spike surface glycoprotein and RNA polymerase

ABSTRACT

Introduction: The COVID-19 pandemic originated from the emergence of anovel coronavirus, SARS-CoV-2, which has been intensively studied since its discovery in order to generate the knowledge necessary to accelerate the development of vaccines and antivirals. Of note, many researchers believe there is great potential in systematically identifying host interactors of viral factors already targeted by existing drugs.

Areas Covered: Herein, the authors discuss in detail the only available large-scale systematic study of the SARS-CoV-2-host protein–protein interaction network. More specifically, the authors review the literature on two key SARS-CoV-2 drug targets, the Spike surface glycoprotein, and the RNA polymerase. The authors also provide the reader with their expert opinion and future perspectives.

Expert opinion: Interactions made by viral proteins with host factors reveal key functions that are likely usurped by the virus and, as aconsequence, points to known drugs that can be repurposed to fight viral infection and collateral damages that can exacerbate various disease conditions in COVID-19.

KEYWORDS:

• SARS-CoV-2
• spike protein
• RNA-dependent RNA polymerase
• antiviral drugs discovery
• COVID-19
• SARS-CoV-2-host protein interactome

Article highlights

• SARS-CoV-2 proteins interact with host cell factors, indicating new biological functions for these proteins.

• Drugs that are known to mod-The Spike surface glycoprotein targets the ACE2 receptor at the surface of host cells, inducing membrane fusion and determining tropism.

• The SARS-CoV-2 RNA-dependent RNA polymerase (RdRP or NSP12) synthesizes viral RNA as part of a viral multisubunit assembly named Replication and Transcription Complex (RTC).

• The Spike surface glycoprotein and the RNA-dependent RNA Polymerase are privileged targets for drug discovery.

• Recombinant vaccines with novel vectors show advantages in multiple gene expression, immunogenicity or immunity enhancement and safety.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

B Coulombe is supported by the Bell-Bombardier Chair of Excellence while E Sokullu is the recipient of a postdoctoral fellowship from the Montreal Clinical Research Institute (IRCM).