SARS‐CoV‐2 modulation of RIG‐I‐MAVS signaling: Potential mechanisms of impairment on host antiviral immunity and therapeutic approaches

ABSTRACT

The coronavirus disease 2019 (COVID‐19) is a global infectious disease aroused by RNA virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Patients may suffer from severe respiratory failure or even die, posing a huge challenge to global public health. Retinoic acid‐inducible gene I (RIG‐I) is one of the major pattern recognition receptors, function to recognize RNA viruses and mediate the innate immune response. RIG‐1 and melanoma differentiation‐associated gene 5 contain an N‐terminal caspase recruitment domain that is activated upon detection of viral RNA in the cytoplasm of virus‐infected cells. Activated RIG‐I and mitochondrial antiviral signaling (MAVS) protein trigger a series of corresponding immune responses such as the production of type I interferon against viral infection. In this review, we are summarizing the role of the structural, nonstructural, and accessory proteins from SARS‐CoV‐2 on the RIG‐I‐MAVS pathway, and exploring the potential mechanism how SARS‐CoV‐2 could evade the host antiviral response. We then proposed that modulation of the RIG‐I‐MAVS signaling pathway might be a novel and effective therapeutic strategy to against COVID‐19 as well as the constantly mutating coronavirus. The retinoic acid‐inducible gene I mitochondrial antiviral signaling (RIG‐I‐MAVS) axis is designated as a major signaling pathway in the innate immune response for RNA viruses. This review summarized the role of various proteins derived from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on the RIG‐I‐MAVS pathway and explored the underlying mechanism of SARS‐CoV‐2 to escape the host antiviral response. Regulation of RIG‐I‐MAVS pathway might be a potentially therapeutic strategy to boost immunity against COVID‐19.