The Suppressor of Cytokine Signalling family of proteins and their potential impact on COVID‐19 disease progression

Abstract

Summary The family of Suppressor of Cytokine Signalling (SOCS) proteins plays pivotal roles in cytokine and immune regulation. Despite their key roles, little attention has been given to the SOCS family as compared to other feedback regulators. To date, SOCS proteins have been found to be exploited by viruses such as herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV), Zika virus, respiratory syncytial virus (RSV), Ebola virus, influenza A virus (IAV) and SARS‐CoV, just to name a few. The hijacking and subsequent upregulation of the SOCS proteins upon viral infection, suppress the associated JAK‐STAT signalling activities, thereby reducing the host antiviral response and promoting viral replication. Two SOCS protein family members, SOCS1 and SOCS3 are well‐studied and their roles in the JAK‐STAT signalling pathway are defined as attenuating interferon (IFN) signalling upon viral infection. The upregulation of SOCS protein by SARS‐CoV during the early stages of infection implies strong similarity with SARS‐CoV‐2, given their closely related genomic organisation. Thus, this review aims to outline the plausibility of SOCS protein inhibitors as a potential therapeutic regimen for COVID‐19 patients. We also discuss the antagonists against SOCS protein to offer an overview on the previous ‘successes’ of SOCS protein inhibition in various viral infections that may portray possible clues for COVID‐19 disease management.

IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA

“…However, the ISGs are not the only antiviral factors. Although most ISGs encode proteins capable of inhibiting different stages of the SARS-CoV-2 replication cycle ( 143 , 261 , 262 ), a few ISGs, including SOCS, USP18, and IFI44, can promote viral infection of the host ( 263 – 268 ). It was shown that silencing of IFI44 inhibits viral replication and overexpression of IFI44 promotes viral production due to negative regulation of the IFN-I pathway by IFI44 ( 195 ).…”

SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion

“…Known as PAMPs, these foreign viral molecules trigger the host innate immune system [58,173]. PAMPs are recognized by PRRs which include TLRs and RLRs [15,174]. These interactions activate NF-κB to produce pro-inflammatory cytokines and IRFs that generate type I and III IFNs [175].…”

“…N Packages viral genomic RNA into a helical ribonucleoprotein form. [14] In some patients, COVID-19 can lead to certain severe complications, such as septic shock, multiple organ failure, and the more pronounced acute respiratory distress syndrome [15]. In times of urgent need, drug repositioning represents a feasible approach to combat COVID-19.…”

Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

“…Afflicting more than 530 million individuals accompanied by 6.3 million deaths worldwide, SARS-CoV-2 infection continues to progress at a very rapid rate on a global scale [1]. The zoonotic origin of SARS-CoV-2 has been postulated to be bats, similar to its previous counterpart, SARS-CoV [2]. Despite exacting a lower estimated case fatality rate (3.4%) compared to its predecessors (9.6% for SARS-CoV, and 40% for MERS-CoV), SARS-CoV-2 shows greater transmissibility along with the rapid emergence of new variants [3].…”