SARS-CoV-2 replication process

The SARS-CoV-2 replication process is the multi-step biological cycle through which the virus reproduces within host cells, serving as the fundamental driver of COVID-19 pathogenesis [1]. Following viral entry and uncoating, the viral genomic RNA is translated into two large polyproteins, pp1a and pp1ab, which are cleaved by the viral proteases Mpro (3CLpro) and PLpro into 16 non-structural proteins (nsps) [2]. These nsps form the replicase-transcriptase complex (RTC), a membrane-associated machinery where the RNA-dependent RNA polymerase (RdRp) facilitates the synthesis of genomic and subgenomic RNAs [3]. This replication machinery is the primary target for direct-acting antivirals; for instance, Remdesivir and Molnupiravir target the RdRp to disrupt RNA synthesis, while Nirmatrelvir targets Mpro to block polyprotein processing [4]. Because this process involves multiple highly conserved enzymes, it remains a focal point for therapeutic intervention to reduce viral load and prevent severe disease progression [5]. References: [1] V'kovski, P., et al. (2021) Nature Reviews Microbiology. [2] Zhang, L., et al. (2020) Science. [3] Hillen, H. S., et al. (2020) Nature. [4] NIH (2024) COVID-19 Treatment Guidelines. [5] Malone, B., et al. (2022) Nature Reviews Molecular Cell Biology.

Other names

SARS-CoV-2 life cycleSARS-CoV-2 viral replicationCoronavirus replication cycleSARS-CoV-2 replicative cycle

Inhibition of viral RNA-dependent RNA polymerase (RdRp) to terminate RNA chain elongation or induce lethal mutagenesis; inhibition of the viral main protease (Mpro/3CLpro) to prevent the processing of viral polyproteins into functional non-structural proteins.