Screening for SARS-CoV-2 non-structural protein 14 inhibitors
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome generates 16 distinct non-structural proteins (nsp) that constitute the enzymes and accessory proteins responsible for virus replication once inside a host cell. These protein complexes produce and cap RNA strands that will go on to be translated by the host machinery. Capping the RNA in a manner that is recognized as similar to endogenous mRNA ensures compatibility, lessens RNA degradation rates and lowers the probability of triggering an immune response in the host cell.
In a paper recently uploaded to the preprint server
et al. (April 8
th, 2021), inhibitors of one essential SARS-CoV-2 non-structural protein are explored, with four compounds, in particular, identified as potential antiviral leads that exhibit synergistic effects with antiviral drug remdesivir.
Small molecule inhibitors of SARS-CoV-2 identified by screening
Even as the vaccine rollout continues against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seeking to bring an end to the coronavirus disease 2019 (COVID-19) pandemic, new variants emerge that show immune escape capabilities. Effective and safe drugs thus remain essential to treat severe infections with this virus.
A new preprint, released on the
bioRxiv server, describes the identification of small molecule inhibitors that block the catalytic activity of the crucial viral non-structural protein 5 (nsp5), using a large-scale screening method.
The importance of nsp5
At least nine enzymes of the virus are important for viral proliferation and are thus ideal for the development of antiviral drugs. These enzymes have the same sequence between different coronaviruses, unlike the spike, nucleocapsid and other structural proteins that are less conserved. This makes vaccines based on the latter protei
Discovery of cryptic pocket in SARS-CoV-2 may lead to pan-coronavirus therapies
Coronaviruses have been around for a long time and have caused several recent deadly outbreaks. The most recent is the ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
A new research paper published in the
Biophysical Journal describes a novel binding pocket used by a viral non-structural protein (nsp) to form an activated complex with its partner nsp. In so doing, it may have revealed a common target that may be useful in the development of a broad-spectrum antiviral drug against all coronaviruses.
GSK-3 inhibitors show promise in treating coronavirus infections
Researchers in the United States have suggested a new approach to treating infection with coronaviruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
The study showed that inhibiting phosphorylation of a key structural protein expressed on coronaviruses impaired SARS-CoV-2 infection in human lung epithelial cells.
The team used inhibitors of the host cell protein glycogen synthase kinase 3 (GSK-3) to block phosphorylation of the SARS-CoV-2 nucleocapsid protein that is essential for coronavirus replication.
The researchers also demonstrated that the GSK-3 inhibitor lithium was associated with a significantly reduced risk for COVID-19
Researchers in the United States have successfully delivered a critical structural protein found in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to a human cell line and tracked its localization deep within the cells.