Mutations from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have created multiple variants. Some variants, such as those found in South Africa and Brazil, have caused concern for their potential to evade the immune response. While vaccination efforts are underway, the world is racing against the viruses’ ability to evolve under selective pressure.
Previously approved drugs starting points for COVID-19 therapeutics
Researchers in the United States have identified several clinically approved compounds that could be repurposed for the treatment and prevention of coronavirus disease 2019 (COVID-19).
By screening a commercial library of drugs that have already been approved by international regulatory agencies, the team identified more than 50 compounds that demonstrated some efficacy in blocking the initial stage of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative agent of COVID-19.
The compounds were able to disrupt the binding of a surface viral protein called Spike to its host cell receptor angiotensin-converting enzyme 2 (ACE2).
The use of mammalian cell surface display for rapid characterization of SARS-CoV-2 variants
A research group from the U.S. demonstrated the practicality of a spike display system in order to accelerate vaccine design, but also to swiftly appraise the effects of mutations in emerging strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their results are currently available on the
bioRxiv preprint server.
SARS-CoV-2, the causative agent of the ongoing coronavirus disease (COVID-19), uses its spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2) in order to fuse cell membrane and viral envelope. The key determinant of host tropism is the S1 subunit of the spike glycoprotein, composed of the receptor-binding domain (RBD) and N-terminal domain (NTD).
Study estimates impact of amino acid changes on SARS-CoV-2 infection
New research led by Costas D. Maranas from The Pennsylvania State University predicts amino acid changes to the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would negatively impact binding affinity and subsequent infection into human cells.
Their results were derived from a novel two-step procedure called neural network molecular mechanics/Poisson-Boltzmann surface area (NN MM-GBSA) that calculated binding energy from receptor-binding domain variants to human angiotensin-converting enzyme 2 (ACE2) receptors. The second step would construct a neural network from the findings to predict binding affinity. The team achieved an 82.2% accuracy rate for categorizing amino acid substitutions as helpful or unhelpful in a variant s binding affinity.
Novel protein construct prevents lethal COVID-19 in mice
Researchers in the United States have developed a novel protein that prevented lethal disease among mice infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
The team engineered a soluble, short, and dimeric version of the native host cell receptor that is bound by a surface structure on SARS-CoV-2 called spike during the initial stage of the infection process.
The team – from the Feinberg School of Medicine in Chicago, the University of Chicago, and Northwestern University in Evanston – suspected that a soluble, truncated version of this membrane-bound receptor – called angiotensin-converting enzyme 2 (ACE2) – would serve as a decoy for SARS-CoV-2 spike binding and potentially neutralize infection.