Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

Yuan, Shuofeng; Yin, Xin; Meng, Xiangzhi; Chan, Jasper Fuk‐Woo; Ye, Zi‐Wei; Riva, Laura; Pache, Lars; Chan, Chris Chun-Yiu; Lai, Pok-Man; Chan, Chris; Poon, Vincent Kwok-Man; Lee, Andrew Chak-Yiu; Matsunaga, Naoko; Pu, Yuan; Yuen, Chun-Kit; Cao, Jianli; Liang, Ronghui; Tang, Kaiming; Li, Sheng; Du, Yushen; Xu, Wan; Lau, Chit-Ying; Sit, Ko‐Yung; Au, Wing‐Kuk; Wang, Runming; Zhang, Yuyuan; Tang, Yan-Dong; Clausen, Thomas; Pihl, Jessica; Oh, Juntaek; Sze, Kong-Hung; Zhang, Anna Jinxia; Chu, Hin; Kok, Kin‐Hang; Wang, Dong; Cai, Xuehui; Esko, Jeffrey D.; Hung, Ivan; Li, Ronald Adolphus; Chen, Honglin; Sun, Hongzhe; Jin, Dong Yan; Sun, Ren; Chanda, Sumit K.; Yuen, Kwok‐Yung

doi:10.1038/s41586-021-03431-4

Cited by 178 publications

(201 citation statements)

References 43 publications

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“…Furthermore, although the perceived risk is low, with no evidence of long-term adverse effects in animal models and limited biological plausibility in humans, prior to the current pandemic, no mRNA or DNA based vaccines authorised for use and long-term effects of use of novel vaccination techniques remain unknown. Research into drug therapy remains important including new and repurposed therapy active against SARS-CoV-2 [57,58].…”

Section: Discussionmentioning

confidence: 99%

The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

et al. 2021

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The global drive to vaccinate against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2020 with countries in Europe, Middle East, and North America leading the roll out of a mass-vaccination program. This systematic review synthesised all available English-language guidelines and research regarding mass-vaccination for COVID-19 until 1 March 2021—the first three months of the global mass-vaccination effort. Data were extracted from national websites, PubMed, Embase, Medline and medRxiv, including peer and non-peer review research findings. A total of 15 national policy documents were included. Policies were summarised according to the World Health Organisation (WHO) framework for mass vaccination. All included policies prioritised front-line health care workers and the elderly. Limited information was available regarding staffing, cold chain, communication strategies and infrastructure requirements for effective vaccine delivery. A total of 26 research studies were identified, reporting roll-out strategies, vaccine uptake and reasons for refusal, adverse effects, and real-life estimates of efficacy. Early data showed a reduction in SARS-CoV-2 cases, hospitalisation and deaths in settings with good coverage. Very low rates of vaccine-related serious adverse events were observed. These findings provide an overview of current practice and early outcomes of COVID-19 mass-vaccination, guiding countries where roll-out is yet to commence.

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Section: Discussionmentioning

confidence: 99%

The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

et al. 2021

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“…Furthermore, the FDA approved leprosy drug Clofazimine was identified in an in vitro screen for drugs with anti-SARS-CoV2 activity displayed significant antiviral activity in hamsters ( Yuan et al, 2021 ).…”

Section: Prophylactic Sars-cov-2 Antivirals In Animal Modelsmentioning

confidence: 99%

Animal models of SARS-CoV-2 and COVID-19 for the development of prophylactic and therapeutic interventions

Renn

Bartok

Zillinger

et al. 2021

Pharmacology & Therapeutics

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Infections of the Coronavirus SARS-CoV-2 continue to spread around the globe, causing Coronavirus Disease (COVID)-19. Infected people are at risk of developing acute interstitial pneumonia, which can result in lethal complications, particularly in patients with pre-existing co-morbidities. Novel prophylactic and therapeutic interventions are urgently needed to limit the infection-associated health risk for the population and to contain the pandemic. Animal models are indispensable to assessing the efficacy and safety of potential new antivirals, vaccines, and other innovative therapies, such as nucleic acid agonists of innate immune sensing receptors. In this review, we provide an overview of the commonly used animal models to study SARS-CoV-2 and COVID-19, including a summary of their susceptibility to infection, the spectrum of symptoms elicited, and the potential for drug development in each model. We hope that this review will help researchers to decide on the right model organism to quickly address their specific scientific questions.

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“…The control hamsters were treated with intraperitoneal or intranasal PBS starting at 6h before virus challenge daily until 3dpi (n=10 per group). Five animals per group were sacri ced at 4dpi for viral load quantitation by qRT-PCR, virus titer quantitation by plaque assay, and histopathological studies as described previously 13 . The survival rates and body weight changes of the remaining 5 animals per group were observed until 14dpi or death.…”

Section: Golden Syrian Hamster Model For Sars-cov-2 Infectionmentioning

confidence: 99%

“…The survival rates and body weight changes of the remaining 5 animals per group were observed until 14dpi or death. Immuno uorescence staining for SARS-CoV-2 nucleocapsid protein expression was performed as we described previously 13 . Time-of-drug-addition assay Time-of-drug-addition assay was performed as we described previously to determine the phase(s) of the SARS-CoV-2 replication cycle targeted by H84T-BanLec 26 .…”

Section: Golden Syrian Hamster Model For Sars-cov-2 Infectionmentioning

confidence: 99%

“…Despite the clinical and public health importance of these coronaviruses, effective anti-coronaviral treatment options remain scarce. Broad-spectrum antivirals such as remdesivir, interferons, ribavirin, lopinavir, and clofazimine have shown variable anti-coronaviral activities against one or more of these CoVs in in vitro settings and/or in vivo [11][12][13][14] . Monoclonal or single-domain antibodies are highly active in vitro and/or in vivo, but are generally virus-or even strain-speci c 15,16 .…”

Section: Introductionmentioning

confidence: 99%

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A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo

Markovitz¹,

Chan²,

Oh³

et al. 2021

Preprint

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Coronaviruses have repeatedly crossed species barriers to cause epidemics1. “Pan-coronavirus” antivirals targeting conserved viral components involved in coronavirus replication, such as the extensively glycosylated spike protein, can be designed. Here we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high-mannose found on viral proteins but seldom on healthy human cells2, potently inhibits the highly virulent MERS-CoV, pandemic SARS-CoV-2 and its variants, and other human-pathogenic coronaviruses at nanomolar concentrations. MERS-CoV-infected human DPP4-transgenic mice treated by H84T-BanLec have significantly higher survival, lower viral burden, and reduced pulmonary damage. Similarly, prophylactic or therapeutic H84T-BanLec is effective against SARS-CoV-2 in hamsters. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Time-of-drug-addition assay shows that H84T-BanLec targets virus entry. Real-time structural analysis with high-speed atomic force microscopy depicts multi-molecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity, and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modelling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the activity against SARS-CoV-2 variants and the lack of resistant mutants. The broad-spectrum H84T-BanLec should be clinically evaluated in respiratory viral infections including COVID-19.

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Clofazimine broadly inhibits coronaviruses including SARS-CoV-2

Cited by 178 publications

References 43 publications

The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

The Implementation of Mass-Vaccination against SARS-CoV-2: A Systematic Review of Existing Strategies and Guidelines

Animal models of SARS-CoV-2 and COVID-19 for the development of prophylactic and therapeutic interventions

A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo

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