Citation: Jiacheng Huang, Yujian Yang, Tiefeng Xu, Jianwei Liang, Xin Wang, Guanguan Li, Lihong Liu, Keda Shi, Zhao Lv, Xikui Sun, Chunmei Li, Xumu Zhang, Qifan Zhou, Sidi Yang, Deyin Guo. Synergistic effect of combinational SHEN26 and PF07817883 in SARS-CoV-2 infection .VIROLOGICA SINICA, 2026, 41(5) : 1261-1264.  http://dx.doi.org/10.1016/j.virs.2026.09.006

Synergistic effect of combinational SHEN26 and PF07817883 in SARS-CoV-2 infection

  • Highlights
    1 ATV014 (SHEN26) and PF07817883 exhibited potent synergistic antiviral activity against SARS-CoV-2 in vitro.
    2 In vivo, the combination showed synergistic antiviral and tissue-repair effects superior to either monotherapy.
    3 The therapeutic potential of combining a RdRp inhibitor with a main protease inhibitor as a complementary antiviral strategy.

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  • 10.1016j.virs.2026.09.006-ESM.docx
    1. Allerton, C.M.N., Arcari, J.T., Aschenbrenner, L.M., Avery, M., Bechle, B.M., Behzadi, M.A., Boras, B., Buzon, L.M., Cardin, R.D., Catlin, N.R., Carlo, A.A., Coffman, K.J., Dantonio, A., Di, L., Eng, H., Farley, K.A., Ferre, R.A., Gernhardt, S.S., Gibson, S.A., Greasley, S.E., Greenfield, S.R., Hurst, B.L., Kalgutkar, A.S., Kimoto, E., Lanyon, L.F., Lovett, G.H., Lian, Y., Liu, W., Alsina, L.A.M., Noell, S., Obach, R.S., Owen, D.R., Patel, N.C., Rai, D.K., Reese, M.R., Rothan, H.A., Sakata, S., Sammons, M.F., Sathish, J.G., Sharma, R., Steppan, C.M., Tuttle, J.B., Verhoest, P.R., Wei, L., Yang, Q., Yurgelonis, I., Zhu, Y., 2024. A Second-Generation Oral SARS-CoV-2 Main Protease Inhibitor Clinical Candidate for the Treatment of COVID-19. J. Med. Chem. 67, 13550-13571.

    2. Bai, J., Asakawa, T., Yuan, W., Lin, Y., Ju, H., Xu, D., Yang, M., Li, S., Li, G., Guo, D., Lu, H., Zhang, X., 2025. Efficacy and safety of SHEN26, a novel oral small molecular RdRp inhibitor for COVID-19 treatment: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial. Virol. J. 22, 16.

    3. Cao, L., Li, Y., Yang, S., Li, G., Zhou, Q., Sun, J., Xu, T., Yang, Yang, Liao, R., Shi, Y., Yang, Yujian, Zhu, T., Huang, S., Ji, Y., Cong, F., Luo, Y., Zhu, Y., Luan, H., Zhang, H., Chen, J., Liu, X., Luo, R., Liu, L., Wang, P., Yu, Y., Xing, F., Ke, B., Zheng, H., Deng, X., Zhang, W., Lin, C., Shi, M., Li, C.-M., Zhang, Y., Zhang, L., Dai, J., Lu, H., Zhao, J., Zhang, X., Guo, D., 2022. The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants. Sci. Transl. Med. 14, eabm7621.

    4. Gidari, A., Sabbatini, S., Schiaroli, E., Bastianelli, S., Pierucci, S., Busti, C., Saraca, L.M., Capogrossi, L., Pasticci, M.B., Francisci, D., Gidari, A., Sabbatini, S., Schiaroli, E., Bastianelli, S., Pierucci, S., Busti, C., Saraca, L.M., Capogrossi, L., Pasticci, M.B., Francisci, D., 2023. Synergistic Activity of Remdesivir-Nirmatrelvir Combination on a SARS-CoV-2 In Vitro Model and a Case Report. Viruses 15, 1577.

    5. Hirsch, C., Kreuzberger, N., Skoetz, N., Monsef, I., Kluge, S., Spinner, C.D., Malin, J.J., 2025. Efficacy and safety of antiviral therapies for the treatment of persistent COVID-19 in immunocompromised patients since the Omicron surge: a systematic review. J. Antimicrob. Chemother. 80, 633-644.

    6. Mortezavi, M., Sloan, A., Singh, R.S.P., Chen, L.F., Kim, J.H., Shojaee, N., Toussi, S.S., Prybylski, J., Baniecki, M.L., Bergman, A., Banerjee, A., Allerton, C., Alami, N.N., 2024. Virologic Response and Safety of Ibuzatrelvir, A Novel SARS-CoV-2 Antiviral, in Adults With COVID-19. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 80, 673-680.

    7. Soares, V.C., Moreira, I.B.G., Dias, S.S.G., 2025. SARS-CoV-2 Infection and Antiviral Strategies: Advances and Limitations. Viruses 17, 1064.

    8. Xia, S., Lan, Q., Zhu, Y., Wang, C., Xu, W., Li, Y., Wang, L., Jiao, F., Zhou, J., Hua, C., Wang, Q., Cai, X., Wu, Y., Gao, J., Liu, H., Sun, G., Munch, J., Kirchhoff, F., Yuan, Z., Xie, Y., Sun, F., Jiang, S., Lu, L., 2021. Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation. Signal Transduct. Target. Ther. 6, 288.

    9. Xia, S., Liu, M., Wang, C., Xu, W., Lan, Q., Feng, S., Qi, F., Bao, L., Du, L., Liu, S., Qin, C., Sun, F., Shi, Z., Zhu, Y., Jiang, S., Lu, L., 2020. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343-355.

    10. Zhou, Q., Yang, S., Cao, L., Yang, Y., Xu, T., Chen, Q., Lu, H., Li, Y., Guo, D., Zhang, X., 2023. Preclinical characterization and anti-SARS-CoV-2 efficacy of ATV014: an oral cyclohexanecarboxylate prodrug of 1'-CN-4-aza-7,9-dideazaadenosine C-nucleoside. Signal Transduct. Target. Ther. 8, 27.

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    Synergistic effect of combinational SHEN26 and PF07817883 in SARS-CoV-2 infection

      Corresponding author: Qifan Zhou, zhouqf@sustech.edu.cn
      Corresponding author: Sidi Yang, yang_sidi@gzlab.ac.cn
      Corresponding author: Deyin Guo, guo_deyin@gzlab.ac.cn
    • a. Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou 510005, China;
    • b. Institute of Human Virology, Department of Pathogen Biology and Biosecurity, And Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China;
    • c. Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen 518055, China;
    • d. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China;
    • e. Shenzhen AntiV Pharma Co. Ltd., Shenzhen 518118, China;
    • f. MOE Key Laboratory of Tropical Disease Control, Zhongshan School of Medicine, Sun Yat-sen University Shenzhen Campus, Sun Yat-Sen University, Shenzhen 518107, China

    Abstract: Highlights
    1 ATV014 (SHEN26) and PF07817883 exhibited potent synergistic antiviral activity against SARS-CoV-2 in vitro.
    2 In vivo, the combination showed synergistic antiviral and tissue-repair effects superior to either monotherapy.
    3 The therapeutic potential of combining a RdRp inhibitor with a main protease inhibitor as a complementary antiviral strategy.

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