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In this paper, Shuai Xia et al. improved their previous in-house pan-coronavirus inhibitor EK1 to target the SARS-CoV-2 S protein. Their new optimized inhibitor EK1C4 showed significantly enhanced effectiveness against the SARS virus group in vitro and against HCoV-OC43 in vivo.
Initially, they evaluated many different EK1 derivatives. Extended validation was done only on EK1 and EK1C4.
This study design is similar but smaller than their previous EK1 study (#276).
The administration was consistent.
The selection process was randomized.
The authors used a wide secondary vector (i.e., untreated, EK1C4-treated 0.5, 2, 4, 12, 24 hours pre-infection, and EK1C4-treated 0.5, 2 hours post-infection). Moreover, they used 0.5, 1, and 2 hour EK1-treatment pre-infection groups. Of each of the 12 mice in these groups, they used 1 for a histopathological check after 5 days, 5 for virus titer collection from the brain after 5 days, and the remaining 6 for body weight and survivability observation for 14 days. These details had to be derived from the methods section, the results section, and supplementary documentation because it is not accurately described in the methods section per se.
The survivability was measured for 14 days. Viral load was tested after 5 days.
Within the EK1C4 group, they are complete.
There is no obvious bias.
For example, logistic regression, nonparametric methods.
For example, are clustered data treated independently or are clusters adjusted for, such as different hospitals or litters?
For example, adjustment for age, sex, or comorbidities.
For example, is it an estimated odds ratio, a median difference in detected cases, etc?
For example, confidence intervals, p-values, and/or Bayes factors.
No conclusions can be made for SARS-CoV-2. EK1C4 might improve the survivability from human coronaviruses in general when given as prophylactic or early after infection.
EK1 didn't show histopathological damage in mice in their previous study. EK1C4 was only verified in mouse brain tissues and on different cell lines to be safe. Drug interactions haven't been verified.
EK1C4 treatment 2 hours after infection did not show to improve survivability significantly. Only the 30-minute post-treatment group completely survived 14 days.
The authors do not mention which mouse line they used. They used Balb/c in their previous study for HCoV-OC43 experiments.
The description of their methods seems to be incomplete and inaccurate in certain parts (e.g., the mouse model, and live virus cell lines). The enhanced potential of EK1C4 is clear when comparing its IC50. It is ca. two orders of magnitudes lower than the IC50 of EK1. Nonetheless, it seems to fall in the same group of virostatics that need to be taken as early as possible. That makes it impractical for a disease with such long incubation times as SARS-CoV-2. The EK1C4 peptide clearly targets the S protein but no controls were used to countercheck co-interactions with other proteins of SARS-CoV-2.
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Title: 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
Please paste a link to the paper or a citation here:
Link: https://www.nature.com/articles/s41422-020-0305-x
What is the paper's Manubot-style citation?
Citation: doi:10.1038/s41422-020-0305-x
Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19
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