Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L.

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 µM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 µM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.

Erratum: Patients' Attitudes to Unproven Therapies in Treating COVID-19 Merit Evaluation.

[This corrects the article DOI: 10.1016/j.xinn.2020.100028.].

Patients' Attitudes to Unproven Therapies in Treating COVID-19 Merit Evaluation.

Since the outbreak of COVID-19, many randomized controlled trials have been launched to test the efficacy of promising treatments. These trials will offer great promise for future treatment. However, a public health emergency calls for a balance between gathering sound evidence and granting therapeutic access to promising trial drugs as widely as possible. In an electronic survey, we found that 3.9% of the participants preferred to receive an unproven trial drug directly in the hypothetical scenario of mild COVID-19 infection. This percentage increased drastically to 31.1% and 54.2% in the hypothetical scenario of severe and extremely severe infection, respectively. Our survey indicates a likelihood of substantial receptivity of trial drugs among actual patients in severe conditions. From the perspective of deontological ethics, a trial can only be approved when potential benefits of the investigational treatment are presumed to outweigh risks, so compassionate or off-label use of investigational therapies merits evaluation.