Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses
Open accessAbstract
Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, β-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E. In cell culture models, treatment of molnupiravir effectively inhibited viral replication and production of infectious viruses of the three seasonal coronaviruses. A time-of-drug-addition experiment indicates the specificity of molnupiravir in inhibiting viral components. Furthermore, combining molnupiravir with the protease inhibitor GC376 resulted in enhanced antiviral activity. Our findings highlight the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.
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Cites
Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results
Pan, H., Peto, R., Karim, Q. A., Alejandria, M. M., Henao-Restrepo, A. M., Garcia, P. J., Kiény, M.-P., Malekzadeh, R., Murthy, S., Préziosi, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2023184 · Cited by 2,748 · see citing works
Identification of a new human coronavirus
van der Hoek, L., Pyrć, K., Jebbink, M. F., Vermeulen-Oost, W., Berkhout, R. J. M., Wolthers, K. C., Dillen, P. M. E. W., Kaandorp, J. C., Spaargaren, J., & Berkhout, B. (2004) · Nature Medicine · doi:10.1038/nm1024 · Cited by 1,868 · see citing works
Sheahan, T. P., Sims, A. M., Zhou, S., Graham, R. L., Pruijssers, A. J. P., Agostini, M. L., Leist, S. R., Schäfer, A., Dinnon, K. H., Stevens, L. J., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abb5883 · Cited by 1,069 · see citing works
SynergyFinder 2.0: visual analytics of multi-drug combination synergies
Ianevski, A., Giri, A. K., & Aittokallio, T. A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa216 · Cited by 882 · see citing works
Hofmann, H., Pyrc, K., van der Hoek, L., Geier, M., Berkhout, B., & Pöhlmann, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409465102 · Cited by 824 · see citing works
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Fu, L., Ye, F., Feng, Y., Yu, F., Wang, Q., Wu, Y., Zhao, C., Sun, H., Huang, B., Niu, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18233-x · Cited by 544 · see citing works
Fischer, W. A., Eron, J. J., Holman, W., Cohen, M. S., Fang, L., Szewczyk, L. J., Sheahan, T. P., Baric, R. S., Mollan, K. R., Wolfe, C. R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abl7430 · Cited by 531 · see citing works
SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801
Wahl, A. R., Gralinski, L. E., Johnson, C. E., Yao, W., Kovářová, M., Dinnon, K. H., Liu, H., Madden, V. J., Krzystek, H. M., De, C., et al. (2021) · Nature · doi:10.1038/s41586-021-03312-w · Cited by 402 · see citing works
Cox, R. M., Wolf, J. D., & Plemper, R. K. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00835-2 · Cited by 391 · see citing works
Agostini, M. L., Pruijssers, A. J. P., Chappell, J. D., Gribble, J., Lu, X., Andres, E. L., Bluemling, G. R., Lockwood, M. A., Sheahan, T. P., Sims, A. M., et al. (2019) · Journal of Virology · doi:10.1128/jvi.01348-19 · Cited by 328 · see citing works
Toots, M., Yoon, J.-J., Cox, R. M., Hart, M., Sticher, Z. M., Makhsous, N., Plesker, R., Barrena, A. H., Reddy, P. G., Mitchell, D. G., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aax5866 · Cited by 327 · see citing works
Molnupiravir, an Oral Antiviral Treatment for COVID-19Preprint
Fischer, W. A., Eron, J. J., Holman, W., et al. (2021) · medRxiv · doi:10.1101/2021.06.17.21258639 · Cited by 221 · see citing works
Stuyver, L. J., Whitaker, T., McBrayer, T. R., Hernández-Santiago, B. I., Lostia, S., Tharnish, P. M., Ramesh, M., Chu, C. K., Jordan, R., Shi, J., et al. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.1.244-254.2003 · Cited by 200 · see citing works
Urakova, N., Kuznetsova, V., Crossman, D. K., Sokratian, A., Guthrie, D. B., Kolykhalov, A. A., Lockwood, M. A., Natchus, M. G., Crowley, M. R., Painter, G. R., et al. (2017) · Journal of Virology · doi:10.1128/jvi.01965-17 · Cited by 194 · see citing works
A time-of–drug addition approach to target identification of antiviral compounds
Daelemans, D., Pauwels, R., Clercq, E. D., & Pannecouque, C. C. (2011) · Nature Protocols · doi:10.1038/nprot.2011.330 · Cited by 148 · see citing works
Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication
Reynard, O., Nguyen, X.-N., Alazard-Dany, N., Barateau, V., Cimarelli, A., & Volchkov, V. E. (2015) · Viruses · doi:10.3390/v7122934 · Cited by 112 · see citing works
da Veiga, A. B. G., Martins, L. G., Riediger, I. N., Mazetto, A., Debur, M. D. C., & Gregianini, T. S. (2020) · Journal of Medical Virology · doi:10.1002/jmv.26362 · Cited by 58 · see citing works
Cross-reactivity towards SARS-CoV-2: the potential role of low-pathogenic human coronaviruses
Ma, Z., Li, P., Ji, Y., Ikram, A., & Pan, Q. (2020) · The Lancet Microbe · doi:10.1016/s2666-5247(20)30098-7 · Cited by 50 · see citing works
Self-citationLi, P., Liu, J., Ma, Z., Bramer, W. M., Peppelenbosch, M. P., & Pan, Q. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa321 · Cited by 18 · see citing works
Self-citationSystematically Mapping Clinical Features of Infections With Classical Endemic Human Coronaviruses
Li, P., Ikram, A., Peppelenbosch, M. P., Ma, Z., & Pan, Q. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1386 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Barber, R. M., Sorensen, R. J. D., Pigott, D. M., Bisignano, C., Carter, A., Amlag, J. O., Collins, J. K., Abbafati, C., Adolph, C., Allorant, A., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00484-6 · Cited by 298 · see citing works
SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination
Li, P., Wang, Y., Lavrijsen, M., Lamers, M. M., de Vries, A. C., Rottier, R. J., Bruno, M. J., Peppelenbosch, M. P., Haagmans, B. L., & Pan, Q. (2022) · Cell Research · doi:10.1038/s41422-022-00618-w · Cited by 205 · see citing works
Self-citationPaxlovid: Mechanism of Action, Synthesis, and In Silico Study
Marzi, M., Vakil, M. K., Bahmanyar, M., & Zarenezhad, E. (2022) · BioMed Research International · doi:10.1155/2022/7341493 · Cited by 137 · see citing works
Antiviral Drug Discovery for the Treatment of COVID-19 Infections
Ng, T. I., Correia, I., Seagal, J., DeGoey, D. A., Schrimpf, M. R., Hardee, D. J., Noey, E. L., & Kati, W. M. (2022) · Viruses · doi:10.3390/v14050961 · Cited by 97 · see citing works
Masyeni, S., Iqhrammullah, M., Frediansyah, A., Nainu, F., Tallei, T. E., Emran, T. B., Ophinni, Y., Dhama, K., & Harapan, H. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27730 · Cited by 75 · see citing works
Jeong, J. H., Chokkakula, S., Min, S. C., Kim, B. K., Choi, W.-S., Oh, S., Yun, Y. S., Kang, D. H., Lee, O.-J., Kim, E., et al. (2022) · Antiviral Research · doi:10.1016/j.antiviral.2022.105430 · Cited by 74 · see citing works
Ramu, R. (2021) · Bioinformation · doi:10.6026/97320630017932 · Cited by 65 · see citing works
Atmar, R. L., & Finch, N. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02404-21 · Cited by 51 · see citing works
Molnupiravir: A Versatile Prodrug against SARS-CoV-2 Variants
Teli, D., Balar, P. C., Patel, K. P., Sharma, A., Chavda, V. P., & Vora, L. K. (2023) · Metabolites · doi:10.3390/metabo13020309 · Cited by 45 · see citing works
A Pandemic Lesson for Global Lung Diseases: Exacerbations Are Preventable
Cookson, W., Moffatt, M. F., Rapeport, G., & Quint, J. K. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202110-2389ci · Cited by 40 · see citing works
Stegmann, K. M., Dickmanns, A., Heinen, N., Blaurock, C., Karrasch, T., Breithaupt, A., Klopfleisch, R., Uhlig, N., Eberlein, V., Issmail, L., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104293 · Cited by 44 · see citing works
Annadi, A. M., Zahar, N. M. E., El‐Sattar, N. E. A. A., Mohamed, E. H., Mahmoud, S. A., & Attia, M. S. (2022) · RSC Advances · doi:10.1039/d2ra05066h · Cited by 39 · see citing works
Nirmatrelvir exerts distinct antiviral potency against different human coronaviruses
Li, J., Wang, Y., Solanki, K., Atre, R., Lavrijsen, M., Pan, Q., Baig, M. S., & Li, P. (2023) · Antiviral Research · doi:10.1016/j.antiviral.2023.105555 · Cited by 31 · see citing works
Self-citationRepurposing of antiviral drugs for COVID-19 and impact of repurposed drugs on the nervous system
Punekar, M., Kshirsagar, M. M., Tellapragada, C., & Patil, K. (2022) · Microbial Pathogenesis · doi:10.1016/j.micpath.2022.105608 · Cited by 29 · see citing works
SARS-CoV-2 Omicron (B.1.1.529) Variant: A Challenge with COVID-19
Afshar, Z. M., Pirzaman, A. T., Karim, B., Anaraki, S. R., Hosseinzadeh, R., Pireivatlou, E. S., Babazadeh, A., Hosseinzadeh, D., Miri, S. R., Sio, T. T. W., et al. (2023) · Diagnostics · doi:10.3390/diagnostics13030559 · Cited by 29 · see citing works
Younis, H. M., Youssef, A. O., El‐Sheikh, S. M., Sheta, S. M., & Attia, M. S. (2023) · Microchemical Journal · doi:10.1016/j.microc.2023.109297 · Cited by 28 · see citing works
Li, Y., Liu, M., Yan, Y., Wang, Z., Dai, Q., Yang, X., Guo, X., Li, W., Chen, X., Cao, R., et al. (2022) · Viruses · doi:10.3390/v14061142 · Cited by 26 · see citing works
Self-citationHuang, Z., Zhang, P., & Deng, L. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad244 · Cited by 25 · see citing works
Li, P., Wang, Y., Lamers, M. M., Lavrijsen, M., Iriondo, C., de Vries, A. C., Rottier, R. J., Peppelenbosch, M. P., Haagmans, B. L., & Pan, Q. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104132 · Cited by 21 · see citing works
Self-citationWeil, T., Lawrenz, J., Seidel, A., Münch, J., & Müller, J. A. (2022) · Antiviral Research · doi:10.1016/j.antiviral.2022.105343 · Cited by 21 · see citing works
SARS-CoV-2 Resistance to Small Molecule Inhibitors
Lopez, U. M., Hasan, M. M., Havranek, B., & Islam, S. M. (2024) · Current Clinical Microbiology Reports · doi:10.1007/s40588-024-00229-6 · Cited by 20 · see citing works
A hypothesis on designing strategy of effective RdRp inhibitors for the treatment of SARS-CoV-2
Chaube, U. J., Patel, B., & Bhatt, H. G. (2022) · 3 Biotech · doi:10.1007/s13205-022-03430-w · Cited by 9 · see citing works
Shehzadi, K., Yu, M., & Liang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417473 · Cited by 11 · see citing works
Wang, Y., Li, P., Lavrijsen, M., Rottier, R. J., den Hoed, C. M., Bruno, M. J., Kamar, N., Peppelenbosch, M. P., de Vries, A. C., & Pan, Q. (2023) · United European Gastroenterology Journal · doi:10.1002/ueg2.12417 · Cited by 8 · see citing works
Self-citationIbrahim, M. A. A., Shehata, M. N. I., Moussa, N. A. M., Hemia, R. R. A., Elhafez, H. S. M. A., El‐Rahman, M. K. A., Sayed, S. R. M., Sidhom, P. A., Dabbish, E., & Shoeib, T. (2023) · ACS Omega · doi:10.1021/acsomega.3c03215 · Cited by 9 · see citing works
Roles of Sialyl Glycans in HCoV-OC43, HCoV-HKU1, MERS-CoV and SARS-CoV-2 Infections
Sriwilaijaroen, N., & Suzuki, Y. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2635-1_17 · Cited by 8 · see citing works
Zheng, Q., Bao, C., Ji, Y., Li, P., Ma, Z., Wang, X., Meng, Q., & Pan, Q. (2023) · Scientific Reports · doi:10.1038/s41598-023-32619-z · Cited by 8 · see citing works
Self-citationLi, J., Wang, X., Ding, Y., Qin, F., de Lima, S. T. S., Papamichail, L., Schraauwen, R., Forato, J., Claro, I. M., Hua, X., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102646 · Cited by 7 · see citing works
Self-citationKulkarni, P., & Padmanabhan, S. (2022) · Biotechnology Letters · doi:10.1007/s10529-022-03259-6 · Cited by 8 · see citing works
Li, Y., Wang, Y., Li, Y., de Vries, A. C., Li, P., Peppelenbosch, M. P., & Pan, Q. (2023) · Antiviral Research · doi:10.1016/j.antiviral.2023.105674 · Cited by 6 · see citing works
Self-citationBonnac, L. F., Dreis, C. D., Rai, M., & Geraghty, R. J. (2025) · Molecules · doi:10.3390/molecules30020210 · Cited by 5 · see citing works
Conserved Targets to Prevent Emerging Coronaviruses
Lomeli, F. G., Elmaraghy, N., Castro, A., Osuna, C., & Newcomb, L. L. (2022) · Viruses · doi:10.3390/v14030563 · Cited by 4 · see citing works
Pandey, K., Acharya, A., Pal, D., Jain, P., Singh, K. D., Durden, D. L., Kutateladze, T. G., Deshpande, A. J., & Byrareddy, S. N. (2024) · Antiviral Research · doi:10.1016/j.antiviral.2024.105904 · Cited by 3 · see citing works
From Batch to Continuous Flow Synthesis in Enzymatic Process Towards Molnupiravir
Hongnak, S., Vorasin, O., Aunbamrung, P., Techapanalai, S., Tiyasakulchai, T., Sonwong, W., Jaito, N., Thongpanchang, C., Whungsinsujaritb, S., Srikun, O., et al. (2024) · Chemistry - An Asian Journal · doi:10.1002/asia.202401134 · Cited by 2 · see citing works
Feng, X., Yang, X., Hu, X., Liu, Q., Ding, Y., Cao, X., Ma, Z., & Ma, X. (2025) · Virology · doi:10.1016/j.virol.2025.110642 · Cited by 2 · see citing works
Self-citationRepurposing of the nucleoside analogs for influenza
Mee-udorn, P., Narkpuk, J., Jaru-Ampornpan, P., Hongeng, S., Uengwetwanit, T., & Srimongkolpithak, N. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.08.006 · Cited by 2 · see citing works
BIOEQUIVALENCE STUDY OF GENERIC MOLNUPIRAVIR IN HEALTHY VOLUNTEERS
Vasilyuk, V. B., Boroduleva, A. Y., Соболев, П. Д., Никифорова, А. Г., Mozgovaya, V. G., Filon, O. V., Zinkovskaya, A. V., Ignatiev, V. G., MIu, S., Kozlova, I. S., et al. (2023) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2022-10-6-562-572 · Cited by 2 · see citing works
Johnson, M. G., Strizki, J., Jensen, E. H., Cohen, J., Katlama, C., Fishchuk, R., Ponce‐de‐León, A., Fourie, N., Cheng, C., McCoy, D., et al. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.03563-23 · Cited by 2 · see citing works
Oral anti-COVID-19 drugs that were recently evaluated by FDA or EMA: a review
Lorenz, D., & Pawliczak, R. (2022) · Alergologia Polska - Polish Journal of Allergology · doi:10.5114/pja.2022.114394 · Cited by 2 · see citing works
Yılmaz, Y., Gürbüz, M., & Şenler, F. Ç. (2024) · Journal of Ankara University Faculty of Medicine · doi:10.4274/atfm.galenos.2024.68095 · Cited by 1 · see citing works
Broad-spectrum coronavirus inhibition by RSV fusion inhibitors targeting six-helix bundle formation
Chen, W., Ji, M. C., Jung, E., Shin, J. S., Yeh, J., Chen, Z., Zhou, B., & Go, Y. Y. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124357 · Cited by 1 · see citing works
Antiviral nucleoside mimics: the development and future perspective of Molnupiravir
Khalil, A. (2026) · Future Medicinal Chemistry · doi:10.1080/17568919.2026.2684621 · Cited by 1 · see citing works
Nanomedicine “New Food for an Old Mouth”: Novel Approaches for the Treatment of COVID-19
Handali, S., Haririan, I., Vaziri, M., & Dorkoosh, F. A. (2022) · Drug Delivery Letters · doi:10.2174/2210303112666220829125054 · Cited by 1 · see citing works
Joseph, O. O., Dahunsi, S. O., & Okoh, A. (2024) · Gene Reports · doi:10.1016/j.genrep.2024.102032
Molnupiravir Inhibits Replication of Multiple Alphacoronavirus suis Strains in Feline Cells
Doki, T., Shinohara, K., To, K., & Takano, T. (2025) · Pathogens · doi:10.3390/pathogens14080787
- Authors
- Wang, Y., Li, P., Solanki, K., Li, Y., Ma, Z., Peppelenbosch, M. P., Baig, M. S., & Pan, Q.
- Affiliations
- Erasmus MC (NL)
- Indian Institute of Technology Indore (IN)
- Northwest Minzu University (CN)
- Corresponding author
- Baig, Mirza S.
- Pan, Qiuwei
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 564
- Pages
- 33-38
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC8486977
- OpenAlex
- W3204436699
- Cited by
- 46
- References
- 20
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 21 · 2021: 1
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Virology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- China Scholarship Council (201703250073, 201808370170, 201903250082)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91719300)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- molnupiravir, seasonal coronaviruses, RNA-dependent RNA polymerase, drug repurposing, N4-hydroxycytidine, HCoV-NL63, HCoV-OC43, HCoV-229E, antiviral activity, viral replication inhibition, GC376, SARS-CoV-2
- MeSH terms
- Antiviral Agents, Common Cold, Cytidine, Humans, Hydroxylamines, Lactams, Leucine, Protein Binding, Pyrrolidines, RNA-Dependent RNA Polymerase, Seasons, Sulfonic Acids, Virus Replication, Coronavirus Infections, Coronavirus 229E, Human, Coronavirus OC43, Human, Coronavirus NL63, Human, Molecular Docking Simulation
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