The SARS-Coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds
By Y. M. Báez-Santos, Sarah E. St. John, A. Mesecar. Antiviral Research, 2014
772 citations recorded by the source corpus.
Over ten years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (SARS-CoV) emerged from the Guangdong Province of China. Despite the fact that the SARS-CoV pandemic infected over 8,500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat SARS-CoV infections. The recent emergence of the deadly human coronavirus that causes Middle East respiratory syndrome (MERS-CoV) is a sobering reminder that new and deadly coronaviruses can emerge at any time with the potential to become pandemics. Therefore, the continued development of therapeutic and prophylactic countermeasures to potentially deadly coronaviruses is warranted. The coronaviral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), are attractive antiviral drug targets because they are essential for coronaviral replication. Although the primary function of PLpro and 3CLpro are to process the viral polyprotein in a coordinated manner, PLpro has the additional function of stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Therefore, targeting PLpro with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells. This review provides an up-to-date discussion on the SARS-CoV papain-like protease including a brief overview of the SARS-CoV genome and replication followed by a more in-depth discussion on the structure and catalytic mechanism of SARS-CoV PLpro, the multiple cellular functions of SARS-CoV PLpro, the inhibition of SARS-CoV PLpro by small molecule inhibitors, and the prospect of inhibiting papain-like protease from other coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on “ From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/91f8306fbc3a1400f882f21ddf821bec8f8e4965
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Citations in the corpus
- Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV (2020, background): “deubiquitinate host cell proteins such as interferon factor 3 (IRF3) as well as to inactivate the pathway for nuclear factor -light-chain-enhancer of activated B cells (NF-B).(36) This leads to”
- Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein (2017, background): “This loop is involved in substrate binding and is different not only between USPs and CoV PLpros but also among different CoVs (Hu et al., 2005; Ratia et al., 2006; Lei et al., 2014; Báez-Santos et al., 2014, 2015; Lee et al., 2015).”
- Molecular Evolution of Human Coronavirus Genomes (2016, neutral): “Most adaptive events occurred in nsp3, a multifunctional protein which acts as a viral protease and contributes to the suppression of interferon responses through its deubiquitinating and deISGylating activities [49].”