Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study

Küçükgüzel, İlkay; kulabaş, necla; Yesil, Tugce

doi:10.29228/jrp.93

Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study

Necla KULABAŞ, (Marmara Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, İstanbul, Türkiye)

Tuğçe Yeşil DEVECİOĞLU, (Marmara Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, İstanbul, Türkiye)

İlkay KÜÇÜKGÜZEL (Marmara Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, İstanbul, Türkiye)

Journal of research in pharmacy (online)

11 0

Yıl: 2021 Cilt: 25 Sayı: 6 Sayfa Aralığı: 967 - 981 Metin Dili: İngilizce DOI: 10.29228/jrp.93 İndeks Tarihi: 09-02-2022

Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study

Öz:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is characterized by a wide range of symptoms including fever, dry cough, headache, decreased sense of taste and smell, was first identified in Wuhan, China in December 2019. Currently, the nucleoside analog, remdesivir has been approved for emergency use authorization (EUA) by the regulatory agencies for the treatment of COVID-19 patients. The need for new antiviral agents has been continuing due to the some disadvantages of remdesivir. Molnupiravir (MLN) that is developed for the treatment of hepatitis C virus (HCV), have been reported to show antiviral activity against SARS-CoV-2 according to the results of a high throughput screen of nucleoside analogs and also phase II/III clinical trials of MLN is ongoing. In this study, fifty four MLN analogs (twelve of them are found to be reported in the literature whereas forty two of them are novel molecules) against SARS-CoV-2 RdRp were designed and evaluated for their potential antiviral activity by using molecular modelling studies. While among the designed MLN analogs, compound C17 was found to have the best potential inhibitor with -7.3 kcal/mol binding energy that is higher than molnupiravir and its active form EIDD-1931. Therefore, the isobutyric acid ester and monophosphate forms of C17 were also compared to the related MLN derivatives in terms of active site interactions. Lastly, the ten compounds with the best binding affinity including C17 were tested in silico for bioavailability, drug-likeness, ADME and safety profiles and were found to exhibit similar bioavailability and safety profile to MLN.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	kulabaş n, Yesil T, Küçükgüzel İ (2021). Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. , 967 - 981. 10.29228/jrp.93
Chicago	kulabaş necla,Yesil Tugce,Küçükgüzel İlkay Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. (2021): 967 - 981. 10.29228/jrp.93
MLA	kulabaş necla,Yesil Tugce,Küçükgüzel İlkay Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. , 2021, ss.967 - 981. 10.29228/jrp.93
AMA	kulabaş n,Yesil T,Küçükgüzel İ Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. . 2021; 967 - 981. 10.29228/jrp.93
Vancouver	kulabaş n,Yesil T,Küçükgüzel İ Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. . 2021; 967 - 981. 10.29228/jrp.93
IEEE	kulabaş n,Yesil T,Küçükgüzel İ "Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study." , ss.967 - 981, 2021. 10.29228/jrp.93
ISNAD	kulabaş, necla vd. "Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study". (2021), 967-981. https://doi.org/10.29228/jrp.93

APA	kulabaş n, Yesil T, Küçükgüzel İ (2021). Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. Journal of research in pharmacy (online), 25(6), 967 - 981. 10.29228/jrp.93
Chicago	kulabaş necla,Yesil Tugce,Küçükgüzel İlkay Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. Journal of research in pharmacy (online) 25, no.6 (2021): 967 - 981. 10.29228/jrp.93
MLA	kulabaş necla,Yesil Tugce,Küçükgüzel İlkay Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. Journal of research in pharmacy (online), vol.25, no.6, 2021, ss.967 - 981. 10.29228/jrp.93
AMA	kulabaş n,Yesil T,Küçükgüzel İ Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. Journal of research in pharmacy (online). 2021; 25(6): 967 - 981. 10.29228/jrp.93
Vancouver	kulabaş n,Yesil T,Küçükgüzel İ Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study. Journal of research in pharmacy (online). 2021; 25(6): 967 - 981. 10.29228/jrp.93
IEEE	kulabaş n,Yesil T,Küçükgüzel İ "Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study." Journal of research in pharmacy (online), 25, ss.967 - 981, 2021. 10.29228/jrp.93
ISNAD	kulabaş, necla vd. "Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors – an in silico docking and ADMET simulation study". Journal of research in pharmacy (online) 25/6 (2021), 967-981. https://doi.org/10.29228/jrp.93