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. 2021 Jun 14;27(22):3022–3036. doi: 10.3748/wjg.v27.i22.3022

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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

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Proposed structure diagram of severe acute respiratory syndrome coronavirus 2 and its life cycle in host cells. A: Structural sketch of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); B: Recognition and entry of SARS-CoV-2 into host cell. Transmembrane spike (S) glycoprotein on the surface of SARS-CoV-2 forms a homotrimer to recognize the human host angiotensin converting enzyme 2 (ACE2) receptor. The S protein is specifically cleaved by two mucose-specific serine proteases [recombinant transmembrane protease serine 2 (TMPRSS2) and TMPRSS4] and furine. The subunit of S protein (S1) is released, and another subunit (S2) is exposed and mediates the viral entry into host cells; C: Life cycle of SARS-CoV-2 in host cells. First, the S protein of SARS-CoV-2 binds to ACE2 to form an S protein-ACE2 complex, which directly mediates the cellular entry of virus and the process is facilitated by TMPRSS2, TMPRSS4, and furine. Second, viral RNA is released into host cytoplasm. Open reading frame (ORF) 1a and ORF1ab are translated into large polyproteins by host ribosome, which are further proteolytically cleaved into 16 non-structural proteins (nsps). Viral polymerase protein is assembled by nsps and viral replication/transcription complex (vRTC) is subsequnently formed by polymerase protein and genomic RNA. Third, a negative sense viral RNA is synthesized and used as a template to replicate progeny (+) sense viral genome and transcribes to form various mRNAs. The nucleocapsid protein is translated in the cytoplasm, whereas the S protein, membrane (M) protein, and envelope (E) protein are translated in the endoplasmic reticulum and transported to the Golgi apparatus for further packaging. Finally, a completely new viral particle is assembled by viral RNA-nucleocapsid complex and S, M, and E proteins in endoplasmic reticulum–Golgi intermediate compartment and is released from host cell via exocytosis. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; M: Membrane; E: Envelope; S: Spike; ER: Endoplasmic reticulum; vRTC: Viral replication/transcription complex; ORF: Open reading frame; TMPRSS: Transmembrane protease serine; ACE2: Angiotensin converting enzyme 2.