Quote:

Results

We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations (range: 2–5), otherwise they have a median of 1 mutation (range: 0–3) (p value < 0.001).

Conclusions

These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.

Quote:

Some polymerase inhibitors are currently being tested in clinical studies to target SARS-CoV-2 RdRp, including Favipiravir, Galidesivir, Remdesivir, Ribavirin, Penciclovir, Galidesivir and Ponatinib. Additionally, other drugs such as Simeprevir (FDA approved HCV protease inhibitor), as well as Filibuvir and Tegobuvir (both RdRp inhibitors), are predicted to bind RdRp by molecular docking studies. In particular, a putative docking site was identified in a hydrophobic cleft very close to the mutated site 323 (P to L), corresponding to mutation 14408 identified in our study. Naturally occurring mutations in RdRp can potentially lead to drug-resistance phenomena, as already observed previously. Alternatively, it might induce a significant decrease in drug-RdRp complex binding affinity. This could lead to different effectiveness of antiviral treatments where mutation 14408 is present. For this reason, due to the high frequency of RdRp mutation in the infected population, it is important to characterize the impact of 14408 mutation on the activity of RdRp and its susceptibility to antiviral drugs.

justme wrote:

Can someone explain why some countries have a much lower death rate (deaths per million) than others while ignoring data from the Communist countries? For example why is Singapore so low. Then explain why are states on the east coast so much higher. I am not sure of the reason, but something is not right. This is a link to the official scoreboard. I would think there would be more uniformity between countries with modern health care.

https://www.worldometers.info/coronavirus/

wilber1 wrote:



For one thing, places like Singapore, Taiwan, Hong Kong etc are small, two of them are completely islands and unlike states, all of them have control over their own borders. New Zealand also has a very low rate. It is also a small island country that came down on the virus early and hard.

BCSnob wrote:

There are underlying health conditions that impact the severity of the disease Covid-19 such as diabetes; the rates of these underlying conditions within a population vary from nation to nation.

CDC: covid underlying conditions

Previously of diabetes by nation