Researchers from the National Autonomous University of Mexico (UNAM) studied the genomic sequence of SARS-CoV-2 and found that from its proteins, the virus that causes COVID-19 could be treated with Sofosbuvir , a drug that is used against hepatitis C .
Rodrigo Jácome Ramírez
and Adrián Cruz González , researchers at the Origin of Life Laboratory of the UNAM’s School of Sciences , analyzed the virus through computer programs with which they evaluated the genetic material of the virus that has caused over 400,000 deaths throughout the world . So far, seven coronaviruses that can affect humans have been identified: 229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2 . The latter was studied by Jácome Ramírez, an expert on virus evolution , mainly of the RNA, which are characterized for developing mutations quickly.
RNA viruses, as SARS-CoV-2, as explained by the researcher, have very peculiar characteristics: “They have very high mutation rates and that explains pandemics.
“Coronaviruses have a particular characteristic among RNA viruses : They have edition mechanisms , that is, they are on the only RNA [viruses] known to have an enzyme that helps them once they replicate and make mistakes; they can correct them, and that helps their genomes to be more stable than other RNA viruses.”
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Jácome Ramírez asserts that his research is focused on the analysis of two proteins that help this virus reproduce: replicase , an enzyme that makes copies of the virus’ genome, and exoribonuclease , an enzyme that helps correct mistakes in the virus.
“They are proteins worth studying to generate specific drugs against the virus, as has happened, for instance, with some antiretrovirals – drugs used against HIV – that prevent replicase from working.”
Inside the virus
The surgeon by the Pan American University and doctor in Sciences by the UNAM studied the genomic sequence of SARS-CoV-2 and paid attention to polymerase because it is one of the main “therapeutic targets” since it has been found in all the RNA viruses; this enzyme is considered as “homologous.”
“ Polymerase has a common ancestor. All polymerases are related in evolution, that is, they are all similar in structure ; this is useful to know their structure in detail and hence, look for broad-spectrum drugs that attack one viral group. The idea would be to look for residues, amino acids, fragments of proteins that are conserved not only in the coronavirus but in other pathogen viruses – that cause diseases in humans – and see if we can find drugs that are able to join those amino acids.”
Aware that developing a drug will take quite some time , the researcher said the treatment could be developed from existing drugs .
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“In order to develop a drug, we must find the exact molecule that sticks to the specific target , and then, we must test it, first on animals and then on humans, to make sure it does not have secondary effects . Finding a drug is currently unfeasible because it would take months, years, and a lot of money.”
The model of investigating existing drugs to mitigate the impact of COVID-19 is already being carried out at a global level. For instance, it has been found that hydroxychloroquine and remdesivir could be used against the new virus.
, as explained by the expert, “inhibits in vitro the replication of the virus, that is, it’s in an experimental phase ; there are no conclusive studies that tell us it can help patients with COVID-19 to recover,” In the case of remdesivir, “it sticks to polymerase,” which is the enzyme that replicates the virus.
After observing the anatomy of the virus, Rodrigo Jácome Ramírez proposes on his investigation to combat the crisis that sofosbuvir , a drug used against hepatitis C, which is also an RNA virus, could work against SAR-CoV-2 .
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“What we did at the laboratory was to superimpose the structures of the enzymes that replicate the virus and we found that sofosbuvir could stick to the replicase in SARS-CoV-2. We would have to perform experiments , but on the computer, it would seem that the place where the drug sticks is present both in hepatitis C and SARS-CoV-2.”
The also professor of the Evolution Biology department stressed that his research is based on “ computer experiments ” from observing the similarities between the replicase in SARS-CoV-2 and hepatitis C.
“With the help of special [computer] programs, we superimposed the replicase in SARS-C over that in hepatitis C and it was observed that sofosbuvir sticks quite well, which helps infer the drug could help on its treatment. This is on a molecular level; there have been no experiments to prove it, but that’s the plan, to use different disciplines to try to contribute.”
In the investigation, Adrián Cruz González focused on exoribonuclease, an interesting therapeutic target: “If we can attack this enzyme, we could remove the virus defense mechanism” said Jácome Ramírez.
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The researcher adds that “ exoribonuclease is very rare among RNA viruses; we have also studied where they took it from in their evolution and, by comparing sequences and structures with those of MERS-CoV and SARS-CoV , we can infer which will be the most adequate places to develop drugs.”
Nevertheless, the investigation, he says, would not contribute to the development of a vaccine but rather toward treatments , that is, the development of an antiviral . “With this, we propose to stop replicating the virus so that the patient can recover . This is not related to vaccine development but with the development of drugs . The vaccine would have to focus, mainly, in the Spike protein , which is the one that sticks to cell receptors and that has to be studied from head to toes to understand how we can develop a vaccine.”
Mexican research
The research by UNAM experts joins the great number of current studies in the world.
“They are unprecedented efforts ,” says Rodrigo Jácome Ramírez; however, he mentions that there are insufficient resources in Mexico because “there have been cuts to sciences, obstacles due to all the problems at the CONACyT , but we’re working with what we have; we do our best to compete with global-class laboratories.”
Moreover, he mentioned that there are independent efforts in Mexico although “there has not been a voice in the government that says that we’re going to do this or that; and not only that, virology in Mexico is a fertile field; there is few infrastructures, regional centers to detect viruses. We’re very unprotected from this kind of circumstances.”
Meanwhile, the UNAM research was published on Nature under the title “ Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic .”
“We’re trying to promote the idea to see if someone adopts it and can begin clinical trials on the drug, knowing that it exists and its toxic profiles and secondary effects are known because it’s not in our field to prove new drugs; our laboratory is focused on IT ,” he asserts.
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