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.

Keywords: Sars-CoV-2; cell death; pathways.

FIGURE 1

Illustration of the genome of severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARS‐CoV‐2 showing the location of structural proteins, open reading frames (orf1a and orf1ab), accessory proteins which them are known to trigger different forms of cell death. *ORF3b and ORF8b is only present in SARS‐CoV. **ORF10 is only present in SARS‐CoV‐2

FIGURE 2

Summary of the mechanisms that lead to apoptosis triggered by the structural and accessory proteins of severe acute respiratory syndrome coronavirus (SARS‐CoV)

FIGURE 3

Mechanisms associated with autophagy triggered by coronaviruses

FIGURE 4

(a)–Pyroptosis triggered by the 3a protein of SARS‐CoV; (b)—3a protein of SARS‐CoV leads to necroptotic cell death by the ability of the SARS 3a protein to oligomerize and insert into membranes

FIGURE 5

Biomolecular interaction network with genes found by text‐mining analysis

FIGURE 6

Heat map enrichment of death‐related biological process and genes of Sars‐CoV (negative log10 of adjusted p‐value)