Written by Hannah Edstrom
Today’s journal club will be abbreviated reviews of some recently released research on covid-19.
Science is famous for nothing if not moving slowly, but research on the latest coronavirus has been rapid. Clinical trials for potential drugs and vaccines have begun. The virus has moved quickly and upended lives and livelihoods worldwide, but even now, herculean efforts are being made at a unusual pace by fine minds, and research is on the move.
Here is a collection of three papers recently published on covid-19.
Fun fact: In them, I discovered that ‘covid-19’ stands for ‘Corona Virus Disease 2019.’ Yup. I am very on top of things.
1. Bat Sampling Reveals Coronavirus Diversity
Detection of novel coronaviruses in bats in Myanmar. Coronaviruses are many and plenty. Both the common cold and the flu are coronaviruses, as is our new covid-19. This study – published in April but first submitted in December 2019 – notes six variations of a coronavirus, previously unknown, discovered in Myanma bats.
Coronaviruses are single-stranded RNA viruses, and they are commonly zoonotic, infecting both mammals and birds. Bats in particular are hosts, with risks magnified by the fact that they coexist easily with people. Rabies is only the beginning of zoonotic diseases from bats: among them, coronaviruses are nothing new – SARS and MERS both came from bats. Other diseases like ebola can be traced to bats as well.
In this study, oral and rectal swabs as well as guano samples were collected during both wet and dry seasons, and RNA was extracted and sequenced. Across 11 species and over 700 samples taken, about fifty samples from three species contained various coronavirus samples. 7 coronavirus types were detected, 6 of which had never been identified before. Bats are undeniably an ecological necessity, but they are dangerous sources of zoonotic diseases (Valitutto et al., 2020).
2. Visualizing Coronavirus Proteins to Better Attack Them
Structure of the RNA-dependent RNA polymerase from COVID-19 virus. This paper visualizes the structure of RNA polymerases used by covid-19, and uses that information to offer a possible explanation for how remdesivir works.
Remdesivir made the news when the first U. S. novel coronavirus patient recovered when given the drug “for compassionate use” – before any clinical trials, simply because it was a last resort. Covid-19 replicates the RNA polymerase nsp12, which forms a complex with two other proteins and catalyzes viral RNA synthesis.
Electron Microscopy enabled the scientists to visualize nsp12 in 3D. With this model, they identified the protein’s active site, and hypothesized where remdesivir interacts with it. Remdesivir is a nucleotide analog antiviral inhibitor (it works by inhibiting RNA replication), and when it bonds to RNA polymerase nsp12, it causes conformational changes that stop covid-19 from propagating further (Gao et al., 2020). It is currently undergoing clinical trial and if it passes, may become a widely used cure for covid-19.
3. Potential Drug for Covid-19 and it’s Variations
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Covid-19 (here, SARS-CoV-2) is not the first coronavirus to plague humankind, and it will not be the last. Coronaviruses grow well in human airway epithelial (HAE) cells, emerge quickly in the human population (three novel variants in the past twenty years), and tend to vary greatly in treatment and vaccine needs.
Thus, the scientists here pursued a drug with diverse therapeutic capacity.
They picked NHC, a broad-spectrum antiviral known to fight varieties of (unrelated) villains like influenza and ebola. Testing it in both mouse models and HAE cell cultures, they found NHC to be non-toxic to the patient, but lethally mutagenic to covid-19.
And MERS-CoV. And SARS-CoV. And a bunch of other coronaviruses – including strains resistant to remdesivir.
It was observed to reduce virus titer and could function as either a prophylactic or treatment. Now all it needs is some clinical testing (Sheahan et al., 2020).
Gao, Y., Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., … Rao, Z. (2020). Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 7498(April), 1–9.
Sheahan, T. P., Sims, A. C., Zhou, S., Graham, R. L., Pruijssers, A. J., Agostini, M. L., … Baric, R. S. (2020). An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Science Translational Medicine, 5883, 1–21. https://doi.org/10.1126/scitranslmed.abb5883
Valitutto, M. T., Aung, O., Tun, K. Y. N., Vodzak, M. E., Zimmerman, D., Yu, J. H., … Mazet, J. (2020). Detection of novel coronaviruses in bats in Myanmar. PloS One, 15(4), e0230802. https://doi.org/10.1371/journal.pone.0230802