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TMPRSS2 and RNA-Dependent RNA Polymerase Are Effective Targets of Therapeutic Intervention for Treatment of COVID-19 Caused by SARS-CoV-2 Variants (B.1.1.7 and B.1.351).
Lee, Jihye; Lee, JinAh; Kim, Hyeon Ju; Ko, Meehyun; Jee, Youngmee; Kim, Seungtaek.
  • Lee J; Zoonotic Virus Laboratory, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
  • Lee J; Zoonotic Virus Laboratory, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
  • Kim HJ; Zoonotic Virus Laboratory, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
  • Ko M; Zoonotic Virus Laboratory, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
  • Jee Y; CEO office, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
  • Kim S; Zoonotic Virus Laboratory, Institut Pasteur Koreagrid.418549.5, Seongnam, South Korea.
Microbiol Spectr ; 9(1): e0047221, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1352541
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ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of the coronavirus disease 2019 (COVID-19) pandemic, and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development, and this effort was partially successful. Since the beginning of the COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world, and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. Viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development; therefore, the inhibitory effects of transmembrane serine protease 2 (TMPRSS2) and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the United Kingdom and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern. IMPORTANCE The COVID-19 pandemic is causing unprecedented global problems in both public health and human society. While some vaccines and monoclonal antibodies were successfully developed very quickly and are currently being used, numerous variants of the causative SARS-CoV-2 are emerging and threatening the efficacy of vaccines and monoclonal antibodies. In order to respond to this challenge, we assessed antiviral efficacy of small-molecule inhibitors that are being developed for treatment of COVID-19 and found that they are still very effective against the SARS-CoV-2 variants. Since most small-molecule inhibitors target viral or host factors other than the mutated sequence of the viral spike protein, they are expected to be potent control measures against the COVID-19 pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / RNA-Dependent RNA Polymerase / Serine Endopeptidases / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Country/Region as subject: Africa / Europa Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.00472-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / RNA-Dependent RNA Polymerase / Serine Endopeptidases / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Country/Region as subject: Africa / Europa Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.00472-21