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Review
. 2021 Aug;16(8):881-895.
doi: 10.1080/17460441.2021.1909566. Epub 2021 Apr 6.

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

Esen Sokullu  1 , Maxime Pinard  1 , Marie-Soleil Gauthier  1 , Benoit Coulombe  1   2
Affiliations
Review

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

Esen Sokullu et al. Expert Opin Drug Discov. 2021 Aug.

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

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Figures

Figure 1.
Figure 1.
SARS-CoV-2-human protein interaction network
Figure 2.
Figure 2.
Drug-human target network
Figure 3.
Figure 3.
(A) Overall topology of the SARS-CoV-2 spike monomer. SP, signal peptide; NTD, N-terminal domain; RBD, receptor-binding domain; RBM, receptor-binding motif; SD1, subdomain 1; SD2, subdomain 2; FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; TM, transmembrane region; CT, cytoplasmic tail. (B) Overall structure of the SARS-CoV-2 RBD bound to ACE2. ACE2 is shown in green. The SARS-CoV-2 RBD core is shown in cyan and RBM in red. disulfide bonds in the SARS-CoV-2 RBD are shown as sticks and indicated by arrows. The N-terminal helix of ACE2 responsible for binding is labeled. (C) Contacting residues are shown as sticks at the SARS-CoV-2 RBD–ACE2 interfaces. positions in RBD that are involved in ACE2 binding are indicated by red labels. Adapted by permission from Springer Nature, Nature, Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. adapted from Lan et al [15]. with permission of springer nature
Figure 4.
Figure 4.
Model of SARS-CoV-2 Replication and Transcription Complex (RTC) subunits and lists of potential drugs targeting them
See this image and copyright information in PMC

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    2. •• This paper provides the first extensive analysis of protein-protein interactions involving SARS-CoV2 proteins and host factors. The identification of host interactors allows to extract information about drugs that can be repurposed to eventually serve as a treatment for COVID–19

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