Coronaviral Infection and Interferon Response: The Virus-Host Arms Race and COVID-19

Abstract

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented morbidity and mortality worldwide. The host cells use a number of pattern recognition receptors (PRRs) for early detection of coronavirus infection, and timely interferon secretion is highly effective against SARS-CoV-2 infection. However, the virus has developed many strategies to delay interferon secretion and disarm cellular defense by intervening in interferon-associated signaling pathways on multiple levels. As a result, some COVID-19 patients suffered dramatic susceptibility to SARS-CoV-2 infection, while another part of the population showed only mild or no symptoms. One hypothesis suggests that functional differences in innate immune integrity could be the key to such variability. This review tries to decipher possible interactions between SARS-CoV-2 proteins and human antiviral interferon sensors. We found that SARS-CoV-2 actively interacts with PRR sensors and antiviral pathways by avoiding interferon suppression, which could result in severe COVID-19 pathogenesis. Finally, we summarize data on available antiviral pharmaceutical options that have shown potential to reduce COVID-19 morbidity and mortality in recent clinical trials.

Impacts of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review

“…In the case of SARS-CoV-2, studies to identify the PRRs involved in the activation of the innate immune response are still ongoing. It appears that TLRs, RLRs, NLRs, and cyclic GMP-AMP synthase (cGAS) - stimulator of IFN genes (STING) pathway (cGAS-STING pathway) - a mechanism induced when some nucleic acids are present in the cell cytoplasm, are activated, triggering the production of proinflammatory cytokines and IFNs in the early stages of infection [ 58 , 59 ]. However, SARS-CoV-2 has a molecular arsenal capable of limiting PRR signaling, thus limiting the production of inflammatory cytokines and IFNs, allowing the virus to escape the immune system rapidly.…”

Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1

“…During IAV or hCoV attachment and subsequent entry, host cells recognize the invading viral particle via pattern recognition receptors (PRRs) to initiate the secretion of virus-induced antiviral cytokines, chemokines, interferon (IFN), and IFN-stimulated genes (ISGs) ( Wiwie et al., 2019 ; Liu et al., 2022a ). Following host cell infection, IAV and hCoV utilize several strategies to hamper IFN expression ( Hale et al., 2008b ; Evseev and Magor, 2021 ).…”

RNA polymerase inhibitor enisamium for treatment of moderate COVID-19 patients: a randomized, placebo-controlled, multicenter, double-blind phase 3 clinical trial

“…2,3 To date, only the antivirals remdesivir (Veklury) and a combination of nirmatrelvir with ritonavir (Paxlovid) have received emergency use approval (EUA) for COVID-19 treatment by the FDA and EMA and few repurposed drugs have shown clinical efficacy in reducing mortality, the need for mechanical ventilation or improving the clinical status of COVID-19 patients admitted to hospital. 4-6…”

“…2,3 To date, only the antivirals remdesivir (Veklury) and a combination of nirmatrelvir with ritonavir (Paxlovid) have received emergency use approval (EUA) for COVID-19 treatment by the FDA and EMA and few repurposed drugs have shown clinical efficacy in reducing mortality, the need for mechanical ventilation or improving the clinical status of COVID-19 patients admitted to hospital. [4][5][6] Early in the COVID-19 pandemic, the World Health Organization (WHO) identified enisamium (4-(benzylcarbamoyl)-1-methylpyridinium, trade name Amizon ® MAX) as a candidate drug for the treatment of COVID-19. Enisamium is licensed for use in 11 countries, including Ukraine and Russia for the treatment of influenza.…”