COVID-19 pandemic has affected human life worldwide since the first discovery of human SARS-CoV-2 infection. Due to scarce understandings of this novel coronavirus, therapeutic interventions regardless of modern or traditional medicines are implemented according to previous knowledge on other virus outbreaks. Besides antiviral drugs, traditional Chinese medicine has concomitantly shown to alleviate clinical symptoms associated with this disease. Recently, emerging studies also indicate that integrating modern medicine and traditional Chinese medicine (TCM) could bring more significant benefits to COVID-19 patients. This minireview provides a summary on the earliest therapeutic approaches recommended by World Health Organization and approved by China FDA for COVID-19 treatment since the outbreak, which are based on the outcomes obtained from preclinical or clinical trials performed until December 2020. The underlying molecular actions of these medicines on COVID-19 that have progressively revealed are also deliberated here. However, the mechanistic actions of these medicines still required intensive research and clinical investigations as some mechanisms are in silico predicted. Due to the treatment urgency, the main limitation of these studies is small group of patients in the trials. Nevertheless, they serve as an important stepping stone for further therapeutic intervention.
KEYWORDS:
Coronavirus; Modern medicine; Traditional Chinese medicine; COVID-19.
Angus, D. C., Derde, L., Al-Beidh, F., Annane, D., Arabi, Y., Beane, A., van Bentum-Puijk, W., Berry, L., Bhimani, Z., Bonten, M., Bradbury, C., Brunkhorst, F., Buxton, M., Buzgau, A., Cheng, A. C., de Jong, M., Detry, M., Estcourt, L., Fitzgerald, M., Goossens, H., Green, C., Haniffa, R., Higgins, A. M.,..., Thomas, A., Keen, A., Digby, S., Cowley, N., Wild, L., Southern, D., Reddy, H., Campbell, A., Watkins, C., Smuts, S., Touma, O., Barnes, N., Alexander, P., Felton, T., Ferguson, S., Sellers, K., Bradley-Potts, J., Yates, D., Birkinshaw, I., Kell, K., Marshall, N., Carr-Knott, L. & Summers, C. 2020. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. Journal of the American Medical Association, 324, 1317-1329.
Baldelli, S., Corbellino, M., Clementi, E., Cattaneo, D. & Gervasoni, C. 2020. Lopinavir/ritonavir in COVID-19 patients: Maybe yes, but at what dose? Journal of Antimicrobial Chemotherapy, 75(9), 2704-2706.
Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., Hohmann, E., Chu, H. Y., Luetkemeyer, A., Kline, S., de Castilla, D. L., Finberg, R. W., Dierberg, K., Tapson, V., Hsieh, L., Patterson, T. F., Paredes, R., Sweeney, D. A., Short, W. R., Touloumi, G., Lye, D. C., Ohmagari, N., Oh, M., Ruiz-Palacios, G. M., Benfield, T., Fätkenheuer, G., Kortepeter, M. G., Atmar, R. L., Creech, C. B., Lundgren, J., Babiker, A. G., Pett, S., Neaton, J. D., Burgess, T. H., Bonnett, T., Green, M., Makowski, M., Osinusi, A., Nayak, S. & Lane, H. C. 2020. Remdesivir for the treatment of Covid-19- Final report. New England Journal of Medicine, 383, 1813-1826.
Bougakov, D., Podell, K. & Goldberg, E. 2020. Multiple neuroinvasive pathways in COVID-19. Molecular Neurobiology, 58(2):564-575.
Brown, A. J., Won, J. J., Graham, R. L., Dinnon, K. H. 3rd, Sims, A. C., Feng, J. Y., Cihlar, T., Denison, M. R., Baric, R. S. & Sheahan, T. P. 2019. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Research, 169, 104541-104541.
Cao, B., Wang, Y., Wen, D., Liu, W., Wang, J., Fan, G., Ruan, L., Song, B., Cai, Y., Wei, M., Li, X., Xia, J., Chen, N., Xiang, J., Yu, T., Bai, T., Xie, X., Zhang, L., Li, C., Yuan, Y., Chen, H., Li, H., Huang, H., Tu, S., Gong, F., Liu, Y., Wei, Y., Dong, C., Zhou, F., Gu, X., Xu, J., Liu, Z., Zhang, Y., Li, H., Shang, L., Wang, K., Li, K., Zhou, X., Dong, X., Qu, Z., Lu, S., Hu, X., Ruan, S., Luo, S., Wu, J., Peng, L., Cheng, F., Pan, L., Zou, J., Jia, C., Wang, J., Liu, X., Wang, S., Wu, X., Ge, Q., He, J., Zhan, H., Qiu, F., Guo, L., Huang, C., Jaki, T., Hayden, F. G., Horby, P. W., Zhang, D. & Wang, C. 2020. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. New England Journal of Medicine, 382, 1787–1799.
Chen, J., Lin, S., Niu, C. & Xiao, Q. 2020a. Clinical evaluation of Shufeng Jiedu capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19: A retrospective study. Expert Review of Respiratory Medicine, 15(2):257-265.
Chen, J., Ling, Y., Xi, X., Liu, P., Li, F., Li, T., Shang, Z., Wang, M., Shen, Y. & Lu, H. 2020b. Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia. Chinese Journal of Infectious Disease, 38, E008-E008.
Cheng, D. Z. & Li, Y. 2020. Clinical effectiveness and case analysis in 54 NCP patients treated with Lanhuaqingwen granules. World Chinese Medicine, 15, 150-154.
Cheng, Z. J. & Shan, J. 2020. 2019 Novel coronavirus: Where we are and what we know. Infection, 48(2), 155-163.
Coutard, B., Valle, C., de Lamballerie, X., Canard, B., Seidah, N. G. & Decroly, E. 2020. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Research, 176, 104742.
Deng, Y-J., Liu, B-W., He, Z-X., Liu, T., Zheng, R-L., Yang, A-D., Huang, A., Li, Y-T. & Xu, Y-L. 2020. Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking. Chinese Traditional Herbal Drugs, 5(51), 1113-1122.
Dequin, P. F., Heming, N., Meziani, F., Plantefève, G., Voiriot, G., Badié, J., François, B., Aubron, C., Ricard, J.D., Ehrmann, S., Jouan, Y., Guillon, A., Leclerc, M., Coffre, C., Bourgoin, H., Lengellé, C., Caille-Fénérol, C., Tavernier, E., Zohar, S., Giraudeau, B., Annane, D., Le Gouge, A. CAPE COVID Trial Group & the CRICS-TriGGERSep Network. 2020. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A randomized clinical trial. Journal of the American Medical Association, 324, 1298-1306.
Ding, Y., Zeng, L., Li, R., Chen, Q., Zhou, B., Chen, Q., Cheng, P. L., Yutao, W., Zheng, J., Yang, Z. & Zhang, F. 2017. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Complementary & Alternative Medicine, 17, 130.
Ferner, R. E., DeVito, N. & Aronson, J. K. 2020. Drug vignettes: Dexamethasone. https://www.cebm.net/covid-19/dexamethasone/. Last accessed on 28 May 2021.
Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Mailhe, M., Doudier, B., Coujon, J., Giordanengo, V., Vieira, V. E., Dupont, H. T., Honore, S., Colson, P., Chabriere, E., La Scola, B., Rolain, J. M., Brouqui, P. & Raoult, D. 2020. Hydrochloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, 56(1), 105949.
Guan, W. J., Ni, Z.Y., Hu, Y., Liang, W. H., Ou, C. Q., He, J. X., Liu, L., Shan, H., Lei, C-L., Hui, D. S.C., Du, B., Li, L-J., Zeng, G., Yuen, K-Y., Chen, R-C., Tang, C-L., Wang, T., Chen, P-Y., Xiang, J., Li, S-Y., Wang, J-L., Liang, Z-J., Peng, Y-X., Wei, L., Liu, Y., Hu, Y-H., Peng, P., Wang, J-M., Liu, J-Y., Chen, Z., Li, G., Zheng, Z-J., Qiu, S-Q., Luo, J., Ye, C-J., Zhu, S-Y. & Zhong, N-S. 2020. Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine, 382, 1708-1720.
He, T. M., Duan, C. C., Li, X. F. & Zhang, J. Y. 2020. Potential mechanism of Xuebijing injection in treatment of coronavirus pneumonia based on network pharmacology and molecular docking. Chinese Journal of Modern Applied Pharmacy, 37(4), 398-405.
Henderson, L. A., Canna, S. W., Schulert, G. S., Volpi, S., Lee, P. Y., Kernan, K. F., Caricchio, R., Mahmud, S., Hazen, M. M., Halyabar, O., Hoyt, K. J., Han, J., Grom, A. A., Gattorno, M., Ravelli, A., De Benedetti, F., Behrens, E. M., Cron, R. Q. & Nigrovic, P. A. 2020. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatology, 72(7). 1059-1063.
Hoffmann, M., Kleine-Weber, H. & Pohlmann, S. 2020. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Molecular Cell, 78, 779–784.
Hu, K., Guan, W. J., Bi, Y., Zhang, W., Li, L., Zhang, B., Liu, Q., Song, Y., Li, X., Duan, Z., Zheng, Q., Yang, Z., Liang, J., Han, M., Ruan, L., Wu, C., Zhang, Y., Jia, Z. H. & Zhong, N. S. 2021. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: a multicenter, prospective, randomized controlled trial. Phytomedicine, 85, 153242.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Gao, H., Guo, L., Xie, J., Wang, G., Jiang, R., Gao, Z., Jin, Q., Wang, J. & Cao, B. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506.
Hung, I. F-N., Lung, K-C., Tso, E. Y-K., Liu, R., Chung, T. W-H., Chu, M-Y., Ng, Y-Y., Lo, J., Chan, J., Tam, A. R., Shum, H-P., Chan, V., Wu, A. K-L., Sin, K-M., Leung, W-S., Law, W-L., Lung, D. C., Sin, S., Yeung, P., Yip, C C-Y., Zhang, R. R., Fung, A. Y-F., Yan, E. Y-W., Leung, K-H., Ip, J. D., Chu, A. W-H., Chan, W-M., Ng, A. C-K., Lee, R., Fung, K., Yeung, A., Wu, T-C., Chan, J. W-M., Yan, W-W., Chan, W-M., Chan, J. F-W., Lie, A. K-W., Tsang, O T-Y., Cheng, V. C-C., Que, T-L., Lau, C-S., Chan, K-H., To, K. K-W. & Yuen, K-Y. 2020. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, Phase 2 trial. Lancet, 395(10238), 1695-1704.
Ji, S., Bai, Q., Wu, X., Zhang, D. W., Wang, S., Shen, J. L. & Fei, G. H. 2020. Unique synergistic antiviral effects of Shufeng Jiedu capsule and oseltamivir in influenza A viral-induced acute exacerbation of chronic obstructive pulmonary disease. Biomedicine & Pharmacotherapy, 121, 109652.
Kageyama, Y., Aida, K., Kawauchi, K., Morimoto, M., Ebisui, T., Akiyama, T. & Nakamura, T. 2020. Jinhua Qinggan granule, a Chinese herbal medicine against COVID-19, induces rapid changes in the plasma levels of IL-6 and IFN-γ. medRxiv 2020.06.08.20124453.
Lane, J. C. E., Weaver, J., Kostka, K., Duarte-Salles, T., Abrahao, M. T. F., Alghoul, H., Alser, O., Alshammari, T. M., Biedermann, P., Burn, E., Casajust, P., Conover, M., Culhane, A. C., Davydov, A., DuVall, S. L., Dymshyts, D., Bertolín, S. F., Fišter, K., Hardin, J., Hester, L., Hripcsak, G., Kent, S., Khosla, S., Kolovos, S., Lambert, C. G., ver der Lei, J., Londhe, A. A., Lynch, K. E., Makadia, R., Margulis, A. V., Matheny, M. E., Mehta, P., Morales, D. R., Morgan-Stewart, H., Mosseveld, M., Newby, D., Nyberg, F., Ostropolets, A., Park, R. W., Prats-Uribe, A., Rao, G. A., Reich, C., Reps, J., Rijnbeek, P., Sathappan, S. M. K., Schuemie, M., Seager, S., Sena, A., Shoaibi, A., Spotnitz, M., Suchard, M. A., Swerdel, J., Torre, C. O., Vizcaya, D., Wen, H., de Wilde, M., You, S.C., Zhang, L., Zhuk, O., Ryan, P. & Prieto-Alhambra, D. 2020. Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid widespread use for COVID-19: a multinational, network cohort and self-controlled case series study. medRxiv doi.org/10.1101/2020.04.08.20054551.
Li, C., Wang, P., Li, M., Zheng, R., Chen, S., Liu, S., Feng, Z., Yao, Y. & Shang, H. 2021. The current evidence for the treatment of sepsis with Xuebijing injection: Bioactive constituents, findings of clinical studies and potential mechanisms. Journal of Ethnopharmacology, 265, 113301.
Li, H., Lu, C. Z. & Tang, K. C. 2004. Clinical observation on treatment of SARS with combination of chaihu droplet pill and huoxiangzhengqi droplet pill. Zhongguo Zhong Xi Yi Jie He Za Zhi, 24, 321-324.
Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., Li, Y., Hu, Z., Zhong, W. & Wang, M. 2020. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery, 6, 16.
Liu, Z., Li, X., Gou, C., Li, L., Luo, X., Zhang, C., Zhang Y, Zhang, J., Jin, A., Li, H., Zeng, Y., Li, T. & Wang, X. 2020. Effect of Jinhua Qinggan granules on novel coronavirus pneumonia in patients. Journal of Traditional Chinese Medicine, 40(3), 467-472.
Luo, H., Gao, Y., Zou, J., Zhang, S., Chen, H., Liu, Q., Tan, D., Han, Y., Zhao, Y., Wang, S. 2020. Reflections on treatment of COVID‑19 with traditional Chinese medicine. Chinese Medicine, 15, 94.
Ma, Q., Qiu, M., Zhou, H., Chen, J., Yang, X., Deng, Z., Chen, L., Zhou, J., Liao, Y., Chen, Q., Zheng, Q., Cai, L., Shen, L. & Yang, Z. 2020. The study on the treatment of Xuebijing injection (XBJ) in adults with severe or critical Corona Virus Disease 2019 and the inhibitory effect of XBJ against SARS-CoV-2. Pharmacological Research, 160, 105073.
Maisonnasse, P., Guedj, J., Contreras, V., Behillil, S., Solas, C., Marlin, R., Naninck, T., Pizzorno, A., Lemaitre, J., Gonçalves, A., Kahlaoui, N., Terrier, O., Fang, R. H.T., Enouf, V., Dereuddre-Bosquet, N., Brisebarre, A., Touret, F., Chapon, C., Hoen, B., Lina, B., Calatrava, M.R., van der Werf, S., de Lamballerie, X. & Le Grand, R. 2020. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates. Nature, 585(7826), 584-587.
Mittal, A., Manjunath, K., Ranjan, R.K., Kaushik, S., Kumar, S. & Verma, V. 2020. COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2. PLoS Pathogens, 16(8), e1008762.
National Institutes of Health. 2020. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/. Last accessed on 16 November 2020.
Ni, L., Chen, L., Huang, X., Han, C., Xu, J., Zhang, H., Luan, X., Zhao, Y., Xu, J., Yuan, W. & Chen, H. 2020. Combating COVID-19 with integrated traditional Chinese and Western medicine in China. Acta Pharmaceutica Sinica B, 10(7), 1149-1162.
Poggiali, E., Zaino, D., Immovilli, P., Rovero, L., Losi, G., Dacrema, A., Nuccetelli, M., Vadacca, G. B., Guidetti, D., Vercelli, A., Magnacavallo, A., Bernardini, S. & Terracciano, C. 2020. Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients. Clinica Chimica Acta, 509, 135-138.
PR Newswire. 2020. TCM Lianhua Qingwen granted first international approval for COVID-19 treatment. https://www.prnewswire.com/news-releases/tcm-lianhua-qingwen-granted-first-international-approval-for-covid-19-treatment-301124374.html. Last accessed on 22 November 2020.
RECOVERY Collaborative Group, Horby, P., Lim, W. S., Emberson, J. R., Mafham, M., Bell, J. L., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., Elmahi, E., Prudon, B., Green, C., Felton, T., Chadwick, D., Rege, K., Fegan, C., Chappell, L. C., Faust, S. N., Jaki, T., Jeffery, K., Montgomery, A., Rowan, K., Juszczak, E., Baillie, J. K., Haynes, R. & Landray, M. J. 2020. Dexamethasone in hospitalized patients with Covid-19– Preliminary report. New England Journal of Medicine, 384(8), 693-704.
Ren, Y., Yin, Z., Dai, J., Yang, Z., Ye, B., Ma, Y., Zhang, T. & Shi, Y. 2020. Evidence-based complementary and alternative medicine exploring active components and mechanism of Jinhua Qinggan Granules in treatment of COVID-19 based on virus-host interaction. Natural Product Communications, 15(9), 1-11.
Runfeng, L., Yunlong, H., Jicheng, H., Weiqi, P., Qinhai, M., Yongxia, S., Chufang, L., Jin, Z., Zhenhua, J., Haiming, J., Kui, Z., Shuxiang, H., Jun, D., Xiaobo, L., Xiaotao, H., Lin, W., Nanshan, Z. & Zifeng, Y. 2020. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacological Research, 156, 104761.
Schoergenhofer, C., Jilma, B., Stimpfl, T., Karolyi, M. & Zoufaly, A. 2020. Pharmacokinetics of lopinavir and ritonavir in patients hospitalized with coronavirus disease 2019 (COVID-19). Annals of Internal Medicine, 173(8), 670-672.
Spinner, C. D., Gottlieb, R. L., Criner, G. J., López, J. R. A., Cattelan, A. M., Soriano Viladomiu, A., Ogbuagu, O., Malhotra, P., Mullane, K. M., Castagna, A., Chai, L. Y. A., Roestenberg, M., Tsang, O. T. Y., Bernasconi, E., Le Turnier, P., Chang, S. C., SenGupta, D., Hyland, R. H., Osinusi, A. O., Cao, H., Blair, C., Wang, H., Gaggar, A., Brainard, D. M., McPhail, M. J., Bhagani, S., Ahn, M. Y., Sanyal, A. J., Huhn, G., Marty, F. M. & GS-US-540-5774 Investigators. 2020. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: A randomized clinical trial. Journal of the American Medical Association, 324(11), 1048-1057.
Tomazini, B. M., Maia, I. S., Cavalcanti, A. B., Berwanger, O., Rosa, R. G., Veiga, V. C., Avezum, A., Lopes, R. D., Bueno, F. R., Silva, M. V. A. O., Baldassare, F. P., Costa, E. L. V., Moura, R. A. B., Honorato, M. O., Costa, A. N., Damiani, L. P., Lisboa, T., Kawano-Dourado, L., Zampieri, F. G., Olivato, G. B., Righy, C., Amendola C. P., Roepke, R. M. L., Freitas, D. H. M., Forte, D. N., Freitas, F. G. R., Fernandes, C. C. F., Melro, L. M. G., Junior, G. F. S., Morais, D. C., Zung, S., Machado, F. R., Azevedo, L. C. P., & COALITION COVID-19 Brazil III Investigators. 2020. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX randomized clinical trial. Journal of the American Medical Association, 324(13), 1307-1316.
Tong, T., Wu, Y. Q., Ni, W. J., Shen, A. Z. & Liu, S. 2020. The potential insights of Traditional Chinese Medicine on treatment of COVID-19. Chin Med, 15, 51.
Wang, C. H., Zhong, Y., Zhang, Y., Liu, J. P., Wang, Y. F., Jia, W. N., Wang, G. C., Li, Z., Zhu, Y. & Gao, X. M. 2016. A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components. Molecular BioSystems, 12, 606-613.
Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hu, Z., Zhong, W., Xiao, G. 2020a. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research, 30(3), 269-271.
Wang, N., Han, S., Liu, R., Meng, L., He, H., Zhang, Y., Wang, C., Lv, Y., Wang, J., Li, X., Ding, Y., Fu, J., Hou, Y., Lu, W., Ma, W., Zhan, Y., Dai, B., Zhang, J., Pan, X., Hu, S., Gao, J., Jia, Q., Zhang, L., Ge, S., Wang, S., Liang, P., Hu, T., Lu, J., Wang, X., Zhou, H., Ta, W., Wang, Y., Lu, S. & He, L. 2020b. Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV spike pseudotyped virus. Phytomedicine, 79, 153333.
Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., Fu, S., Gao, L., Cheng, Z., Lu, Q., Hu, Y., Luo, G., Wang, K., Lu, Y., Li, H., Wang, S., Ruan, S., Yang, C., Mei, C., Wang, Y., Ding, D., Wu, F., Tang, X., Ye, X., Ye, Y., Liu, B., Yang, J., Yin, W., Wang, A., Fan, G., Zhou, F., Liu, Z., Gu, X., Xu, J., Shang, L., Zhang, Y., Cao, L., Guo, T., Wan, Y., Qin, H., Jiang, Y., Jaki, T., Hayden, F.G., Horby, P. W., Cao, B. & Wang, C. 2020c. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 395(10236), 1569-1578.
Williamson, B. N., Feldmann, F., Schwarz, B., Meade-White, K., Porter, D. P., Schulz, J., van Doremalen, N., Leighton, I., Yinda, C. K., Pérez-Pérez, L., Okumura, A., Lovaglio, J., Hanley, P. W., Saturday, G., Bosio, C. M., Anzick, S., Barbian, K., Cihlar, T., Martens, C., Scott, D. P., Munster, V. J. & de Wit, E. 2020. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature, 585(7824), 273-276.
World Health Organization. 2021. WHO Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int/. Last accessed on 8 April 2021.
World Health Organization. 2020. WHO supports scientifically proven traditional medicine. https://www.afro.who.int/news/who-supports-scientifically-proven-traditional-medicine. Last accessed on 21 November 2020.
Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X., Niu, P., Meng, J., Zhu, Z., Zhang, Z., Wang, J., Sheng, J., Quan, L., Xia, Z., Tan, W., Cheng, G. & Jiang, T. 2020a, Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe, 27(3), 325-328.
Wu, H., Wang, J. Q., Yang, Y. Y., Li, T. Y., Cao, Y. J., Qu, Y. X., Jin, Y. J., Zhang, C. N. & Sun, Y. K. 2020b. Preliminary exploration of the mechanism of Qingfei Paidu decoction against novel coronavirus pneumonia based on network pharmacology and molecular docking technology. Yaoxue Xuebao, 55(3), 374-83.
Xia, L., Shi, Y., Su, J., Friedemann, T., Tao, Z., Lu, Y., Ling, Y., Lv, Y., Zhao, R., Geng, Z., Cui, X., Lu, H. & Schröder, S. 2021. Shufeng Jiedu, a promising herbal therapy for moderate COVID-19: Antiviral and anti-inflammatory properties, pathways of bioactive compounds, and a clinical real-world pragmatic study. Phytomedicine, 85, 153390.
Xiao, M., Tian, J., Zhou, Y., Xu, X., Min, X., Lv, Y., Peng, M., Zhang, Y., Yan, D., Lang, S., Zhang, Q., Fan, A., Ke, J., Li, X., Liu, B., Jiang, M., Liu, Q., Zhu, J., Yang, L., Zhu, Z., Zeng, K., Li, C., Zheng, Y., Wu, H., Lin, J., Lian, F., Li, X. & Tong, X. 2020. Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial. Pharmacological Research, 161, 105126.
Xin, S., Cheng, X., Zhu, B., Liao, X., Yang, F., Song, L., Shi, Y., Guan, X., Su, R., Wang, J., Xing, L., Xu, X., Jin, L., Liu, Y., Zhou, W., Zhang, D., Liang, L., Yu, Y. & Yu, R. 2020. Clinical retrospective study on the efficacy of Qingfei Paidu decoction combined with Western medicine for COVID-19 treatment. Biomedicine & Pharmacotherapy, 129, 110500.
Xing, Y., Hua, Y-R., Shang, J., Ge, W-H. & Liao, J. 2020. Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing injection in the treatment of coronavirus disease 2019. Chinese Journal of Natural Medicines, 18(12), 941-951.
Yang, C., Wang, Y., He, J., Yan, W., Jiang, H., Chen, Q., Li, L. & Yang, Z. 2020a. Lianhua-Qingwen displays antiviral and anti-inflammatory activity and synergistic effects with oseltamivir against influenza B virus infection in the mouse model. Evidence-Based Complementary and Alternative Medicine, 2020, 3196375.
Yang, R., Liu, H., Bai, C., Wang, Y., Zhang, X., Guo, R., Wu, S., Wang, J., Leung, E., Chang, H., Li, P., Liu, T. & Wang, Y. 2020b. Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In silico and experimental study. Pharmacological Research, 157, 104820.
Zhuang, W., Fan, Z., Chu, Y., Wang, H., Yang, Y., Wu, L., Sun, N., Sun, G., Shen, Y., Lin, X., Guo, G. & Xi, S. 2020. Chinese patent medicines in the treatment of coronavirus disease 2019 (COVID-19) in China. Frontiers in Pharmacology, 11, 1066.