Cell death mechanisms involved in cell injury caused by SARS‐CoV‐2

Abstract

Coronavirus disease 2019 (Covid‐19) is an emerging novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that rapidly spread worldwide. In addition to lung injury, Covid‐19 patients may develop extrapulmonary symptoms, including cardiac, liver, kidney, digestive tract, and neurological injuries. Angiotensin converting enzyme 2 is the major receptor for the entry of SARS‐CoV‐2 into host cells. The specific mechanisms that lead to cell death in different tissues during infection by SARS‐CoV‐2 remains unknown. Based on data of the previous human coronavirus SARS‐CoV together with information about SARS‐CoV‐2, this review provides a summary of the mechanisms involved in cell death, including apoptosis, autophagy, and necrosis, provoked by severe acute respiratory syndrome coronavirus.

Programmed cell death: the pathways to severe COVID-19?

“…The exact mechanism of SARS-CoV-2 viral spread through the respiratory tract, kinetics of infection and cytokine release are still under investigation. Multiple studies using other coronaviruses [ 8 , 30 , 31 ] have attempted to help fill the gaps in our knowledge of COVID-19 disease pathogenesis. However, although SARS-CoV-2 is in the same Betacoronavirus clade as MERS-CoV and SARS-CoV, there are notable differences between their whole genome and amino acid sequences, with SARS-CoV-2 being closer related to bat coronaviruses than other viruses associated with outbreaks in humans [ 32 , 33 ].…”

“…Coronaviruses are known to engage apoptotic pathways via diverse mechanisms. The SARS-CoV accessory proteins ORFs 3a, 6, 7a, 7b, 8a and 9b, as well as the structural proteins M and N, were associated with apoptosis (reviewed in [ 8 ]), but their relevance during in vivo infection still needs to be clarified. Several studies addressing the role of viral proteins in cell death show they can lead to apoptosis through a variety of signaling events.…”

“…This highlights a critical need for continued efforts to identify the molecular mechanisms underlying COVID-19 disease to improve current treatment options. Inflammation and cell death have been proposed to be central drivers of disease pathology in COVID-19 patients (as reviewed in [ 7 , 8 ]). These reports suggest that targeting host cell death pathways may have therapeutic value in mitigation severe COVID-19.…”

Therapy Targets SARS-CoV-2 Infection-Induced Cell Death

“…The replication of coronaviruses in cells is regulated by many host factors, which can induce drastic structural and physiological changes in cells ( 2 ). During infection, SARS-CoV-2 could induce diverse cell death pathways ( 31 , 32 ), such as apoptosis, necroptosis, pyroptosis, and NETosis in the host cells ( Figure 1B ).…”

Role of ORF8a as accessory protein in apoptosis induction in SARS‐CoV‐2 infection

“…Recently in a published article in Reviews in Medical Virology , Morais da Silva et al., described the different mechanisms that are involved in cell death process such as apoptosis, autophagy, and necrosis which are caused by SARS‐CoV‐2. 1 The authors reported SARS‐CoV and SARS‐CoV‐2 genomes contain eight accessory genes whose open reading frames are interspersed among the structural genes; two between S and E genes (ORFs 3a and 3b), five are located between the M and N genes (6, 7a, 7b, 8a, 8b) and one within the N gene (9b); in addition, the authors presented ORF8a as one of the accessory proteins in both SARS‐CoV and SARS‐CoV‐2 in fig. 1, 1 although scientific evidence show that genome of SARS‐CoV‐2 lacks ORF8a.…”