SARS coronavirus gRNA:RTC:RNA primer binds RTC inhibitors

Stable Identifier
R-HSA-9680262
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
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Remdesivir (GS-5734) is an investigational nucleotide analogue drug that was developed for its broad spectrum antiviral potential against Ebola and Marburg virus activity (Siegel et al. 2017). It targets and inhibitis viral RNA-dependent RNA polymerase (nsp12, RdRP), the key component of the replication transcription complex (RTC) (Agostini et al. 2018, Brown et al. 2019, Gordon et al. 2020). Remdesivir is being investigated for potential antiviral activity against SARS-CoV-2 by targeting viral replication (Agostini et al. 2018). Gordon et al. demonstrate remdesivir possesses broad antiviral activity against RNA viruses, including SARS-CoV, MERS-CoV and SARS-CoV-2 in-vitro (Gordon et al. 2020b). It could prevent asymptomatic, mild or moderate COVID-19 cases from progressing to severe disease (clinical trials NCT04252664, NCT04257656) but results so far in infected people have been mixed.

EIDD-2801, is an isopropylester prodrug of the ribonucleoside analogue N4-hydroxycytidine (NHC, EIDD-1931) that shows broad spectrum antiviral activity against various RNA viruses including Ebola, Influenza and CoV (Toots et al. 2019). NHC acts as a competitive alternative substrate for virally encoded RNA-dependent RNA polymerases. NHC was shown to inhibit multiple genetically-distinct Bat-CoV viruses in human primary epithelial cells without affecting cell viability. Prophylactic/therapeutic oral administration of NHC reduced lung titers and prevented acute lung failure in C57B/6 mice infected with CoV. The potency of NHC against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses (Sheahan et al. 2020).

Literature References
PubMed ID Title Journal Year
31645453 Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia

Toots, M, Yoon, JJ, Cox, RM, Hart, M, Sticher, ZM, Makhsous, N, Plesker, R, Barrena, AH, Reddy, PG, Mitchell, DG, Shean, RC, Bluemling, GR, Kolykhalov, AA, Greninger, AL, Natchus, MG, Painter, GR, Plemper, RK

Sci Transl Med 2019
32094225 The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus

Gordon, CJ, Tchesnokov, EP, Feng, JY, Porter, DP, Gotte, M

J. Biol. Chem. 2020
32258351 Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses

Amirian, ES, Levy, JK

One Health 2020
32284326 Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency

Gordon, CJ, Tchesnokov, EP, Woolner, E, Perry, JK, Feng, JY, Porter, DP, Gotte, M

J. Biol. Chem. 2020
32253226 An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

Sheahan, TP, Sims, AC, Zhou, S, Graham, RL, Pruijssers, AJ, Agostini, ML, Leist, SR, Schäfer, A, Dinnon, KH, Stevens, LJ, Chappell, JD, Lu, X, Hughes, TM, George, AS, Hill, CS, Montgomery, SA, Brown, AJ, Bluemling, GR, Natchus, MG, Saindane, M, Kolykhalov, AA, Painter, G, Harcourt, J, Tamin, A, Thornburg, NJ, Swanstrom, R, Denison, MR, Baric, RS

Sci Transl Med 2020
31233808 Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase

Brown, AJ, Won, JJ, Graham, RL, Dinnon, KH, Sims, AC, Feng, JY, Cihlar, T, Denison, MR, Baric, RS, Sheahan, TP

Antiviral Res. 2019
29511076 Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

Agostini, ML, Andres, EL, Sims, AC, Graham, RL, Sheahan, TP, Lu, X, Smith, EC, Case, JB, Feng, JY, Jordan, R, Ray, AS, Cihlar, T, Siegel, D, Mackman, RL, Clarke, MO, Baric, RS, Denison, MR

mBio 2018
Participants
Participant Of
Disease
Name Identifier Synonyms
severe acute respiratory syndrome 2945 SARS-CoV infection, SARS
Authored
Reviewed
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