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Understanding the SARS-CoV-2 mechanism of diseaseSARS-CoV-2: an introduction

On 31 December 2019, China alerted the World Health Organization (WHO) to several cases of pneumonia with an unknown cause in Wuhan.1 The cases were later found to be caused by an enveloped RNA (ribonucleic acid) virus.2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus, which can lead to the development of coronavirus disease 2019 (COVID-19).3

SARS-CoV-2 virion2

SARS-CoV-2 entry into host cells is mediated by its spike glycoproteins.2

The virus binds to the host cell receptor angiotensin converting enzyme 2 (ACE2) via the receptor binding domain (RBD) in the S1 subunit of the spike glycoprotein.2 

SARS-CoV-2 viral lifecycle

This video covers the key stages of the SARS-CoV-2 lifecycle.

 SARS-CoV-2 viral lifecycle4-5

Adapted from: Eastman RT, et al. ACS Cent Sci 2020;6(5):672–83.

3CLpro: 3-chymotrypsin-like-protease, ACE2: angiotensin converting enzyme 2, RdRP: RNA-dependent RNA polymerase, RNA: ribonucleic acid

Importance of 3CLᵖʳᵒ in the SARS-CoV-2 lifecycle
  • Protease activity is important in viruses. These enzymes cleave viral polyprotein precursors that are essential for viral replication4
  • The 3CL protease (3CLᵖʳᵒ or Mᵖʳᵒ) is an important cysteine protease in SARS-CoV-25
    • Cleavage by 3CLᵖʳᵒ releases nonstructural protein domains (NSPs) 5-16 from the initial polyproteins translated by the virus (using host ribosomes), which form the replication and transcription complex (RTC)5
    • NSP release/RTC formation is essential to replication5
  • 3CLᵖʳᵒ is an attractive target because:
    • It is essential for viral replication6–8
    • The substrate-recognition pocket is highly conserved6,7
    • There is no homologous human protease8
Explore moreLearn more about diagnosing COVID-19

Find out more about COVID-19 diagnosis and patients who may be at high-risk of progression to severe disease.

 Signs & symptoms Loading High risk patients Loading Testing LoadingReferencesReferences:WHO. Listings of WHO’s response to COVID-19. Available from: https://www.who.int/news/item/29-06-2020-covidtimeline. Accessed: September 2022.Yang J, et al. Nat Commun 2020;4541.Shereen MA, et al. J Adv Res 2020;24:91–8.Steinkühler C. Viral Proteases. In: Offermanns S, Rosenthal W (eds). Encyclopedia of Molecular Pharmacology. 2008, Springer, Berlin, Heidelberg. Available from: https://doi.org/10.1007/978-3-540-38918-7_146. Accessed: September 2022.V’kovski P, et al. Nat Rev Microbiol 2021;19:155–70.Tao K, et al. Clin Microbiol Rev 2021;34(4):e0010921.Yang H, et al. PLoS Biol 2005:3(10):e324.Razali R, et al. Microorganisms 2021;9(12):2481.About Treatment options for COVID-19

Find out about the therapeutic targets in the viral lifecycle

 Learn more Loading Vaccine types

Learn about different types of vaccines and how they may prevent disease

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Adverse events should be reported. Reporting forms and information can be found at https://www.pfizersafetyreporting.com/#/en

 

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