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sars-cov-2

4 papers tagged “sars-cov-2

MedicineNew England Journal of Medicine · Dec 2020 Open access

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, et al.

This multinational, randomized, placebo-controlled phase 2/3 trial evaluated the safety and efficacy of two 30-µg doses of the BNT162b2 lipid-nanoparticle mRNA vaccine, given 21 days apart, in 43,548 participants 16 years of age or older. Among those without prior SARS-CoV-2 infection, the vaccine conferred 95% protection against laboratory-confirmed Covid-19 beginning at least 7 days after the second dose. The safety profile over a median of about two months was characterized by short-lived, mostly mild-to-moderate reactions, with a low incidence of serious adverse events comparable to placebo.

BiologyScience · Oct 2020 Open access

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

Longxing Cao, Inna Goreshnik, Brian Coventry and David Baker

The authors used computational de novo protein design to create small, stable miniproteins that bind the SARS-CoV-2 spike receptor-binding domain and block its interaction with ACE2. Two design strategies were used: incorporating the ACE2 helix into a designed scaffold, and building entirely new binders against the RBD. The best designs bound with picomolar affinity and neutralized the virus, with cryo-EM confirming the binding modes matched the computational models.

BiologyNature · Apr 2020 Open access

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

David E. Gordon, Gwendolyn M. Jang and Mehdi Bouhaddou

The authors expressed 26 of the 29 SARS-CoV-2 proteins in human cells and used affinity-purification mass spectrometry to map 332 high-confidence virus-human protein-protein interactions. They then identified 69 existing drugs and compounds that target the human proteins in this interactome and tested several for antiviral activity. Two pharmacological classes (mRNA translation inhibitors and Sigma1/Sigma2 receptor regulators) showed antiviral effects, providing candidate therapeutics for repurposing.

BiologyScience · Feb 2020 Open access

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett, Jory A. Goldsmith, Ching-Lin Hsieh, Olubukola Abiona, et al.

The authors determined a 3.5 angstrom cryo-EM structure of the SARS-CoV-2 (2019-nCoV) spike glycoprotein ectodomain stabilized in the prefusion conformation. They showed the receptor-binding domain engages human ACE2 with roughly 10- to 20-fold higher affinity than the SARS-CoV-1 spike, helping explain efficient human transmission. They also found that SARS-CoV-1 receptor-binding antibodies did not appreciably bind the new spike, informing vaccine and therapeutic design.