Scientists tested 47 old drugs to fight the coronavirus, and the results show promising clues!

May 26, 2020 /
BiovalleyBIOON / -- The more researchers learn about how coronaviruses attach, invade, and hijack human cells, the more effective they can find antiviral drugsTwo months ago, when researchers began mapping coronaviruses, they hoped it was trueThis map shows all coronavirus proteins and all the proteins found in the human body that interact with these viral proteinsin theory, any intersection between a virus and a human protein is where drugs can fight coronavirusesBut instead of trying to develop new drugs to address these interactions, the researchers turned to more than 2,000 unique drugs that have been approved for human use by theFDAThe researchers believe that somewhere on this long list there will be drugs or compounds that interact with human proteins like coronavirusesthe multidisciplinary research team, led by Professor Nevan Krogan, director of the Institute of Quantitative Biological Sciences at the University of California, San Francisco,identified 69 existing drugs and compounds that could treat COVID-19A month ago, they began shipping the drugs to the Pasteur Institute in Paris and Mount Sinai in New York to see if they could really fight the coronavirusover the past four weeks, researchers have tested 47 anti-coronavirus drugs and compounds in the lab, and have identified some strong therapeutic clues and two separate mechanisms for how these drugs affect SARS-CoV-2 infectionThe findings were published recently in Naturepicture source: Naturetesting process
maps developed by researchers and screeningfdadrug catalogs show potential interactions between viruses, human cells and existing drugs or compoundsBut they don't know if the drug they've identified will make a person more resistant to the virus, more susceptible to infection, or any effectto find out, there are three thingssoftwaregarden: drugs, live viruses, and the cells that test themIt is ideal to test the drug in infected human cellsHowever, scientists do not yet know which human cells are best suited to study coronaviruses in the laboratoryInstead, they used African green monkey cells, which are often used to test antiviral drugs instead of human cellsThey are susceptible to coronaviruses and respond very close to human cellsafter infecting the monkey cells with live viruses, their partners in Paris and New York added the drugs identified to half of the cells and kept the other half as a controlThey then measured the number of viruses in the sample and the number of surviving cellsIf there were fewer viruses and more live cells in the sample with the drug than in the control group, this meant that the drug would destroy the virus replicationThe team is also looking at the toxicity of the drugs to cellsafter classifying the results of hundreds of experiments using 47 predictive drugs, their interaction predictions seemed to be correctIn fact, some drugs do fight coronaviruses, while others make cells more susceptible to infection it's important to remember that these are only preliminary findings that haven't been tested on people No one should go out and buy these medicines but the result is interesting for two reasons Not only did the researchers find individual drugs that could fight the coronavirus, or it could make people more susceptible to the virus; researchers identified two groups of drugs that affect the virus, which work in two different ways, one of which has never been described disrupts translation
virus is spread by entering cells, hijacking certain mechanisms of cells and using it to make more copies of the virus These new viruses then continue to infect other cells The first step in this process is for cells to make new viral proteins from viral RNA This is called translation As the researchers browsed the map, they noticed that some viral proteins interacted with the human proteins involved in translation, and that some drugs interacted with those proteins After testing, they found two compounds that disrupted the translation of the virus these two compounds are called ternatin-4 and zotatifin Both drugs are currently used to treat multiple myeloma, and appear to fight COVID-19 by binding to proteins in cells that need to be translated and inhibited Plitidepsin, a molecule similar to ternatin-4, is currently in clinical trials to treat COVID-19 The second drug, zotatifin, acts on another protein involved in translation Researchers are working with the CEO of the company that makes the drug to put it into clinical trials as soon as possible Sigma receptor
the researchers found that the second group of drugs worked in a completely different way cell receptors are present inside and on the surface of all cells They act like special switches When a particular molecule binds to a particular receptor, this tells the cell to do a specific task Viruses usually use receptors to infect cells the researchers' initial map identified two MV cell receptors, Sigma R1 and Sigma R2, that are expected to be used in drug therapy Tests confirmed their suspicions they identified seven drugs or molecules that interact with these receptors Two antipsychotic drugs used to treat schizophrenia, haloperidol and melperone, showed antiviral activity against SARS-CoV-2 Two effective antihistamines, clemastine and cloperastine, as well as the compounds PB28 and estrogen progesterone, also showed antiviral activity remember that so far, all of these interactions have been observed only in monkey cells in a petri dish it is not clear to researchers how viral proteins manipulate Sigma R1 and Sigma R2 receptors They believe that viruses use these receptors to aid replication, so reducing their activity may inhibit replication and reduce infection interestingly, the effect of the seventh compound -- a common ingredient in cough medicine, right meschafen -- is the opposite: its presence contributes to the spread of the virus When the researchers' partners tested infected cells with the compound, the virus was able to replicate more easily and more cells died this may be a very important finding, but the researchers stress that more tests are needed to determine whether COVID-19 patients need to avoid cough syrup containing this ingredient all of these findings are exciting, but they need to be clinical trials, FDA or anyone else to know whether or not to take these drugs to cope with COVID-19 Neither the public, policymakers nor the media should panic and jump to conclusions picture source: Nature another interesting thing to note is that hydroxychloroquine( a controversial drug that shows mixed results in the treatment of COVID-19) can also bind to SigmaR1 and SigmaR2 receptors But according to researchers in both laboratories, they believe hydroxychloroquine is not effectively bound to them researchers have long known that hydroxychloroquine can easily bind to receptors in the heart and cause harm Because of the differences in their binding tendencies, they do not consider hydroxychloroquine to be a reliable treatment Ongoing clinical trials will soon clarify these unknowns the sooner the better the idea of researchers is that by better understanding the interactions of coronaviruses with the human body, they can find treatments in thousands of existing drugs and compounds their ideas Not only were a number of drugs that might have been used to fight SARS-CoV-2, but they also learned how and why they worked but it's not the only exciting thing These proteins used by SARS-CoV-2 to infect and replicate human cells, as well as proteins targeted by these drugs, are also associated with the coronavirus SARS-1 and MERS hijacking for viral replication Therefore, if any of these drugs are effective, they may be effective for COVID-22, COVID-24, or any COVID that may occur in the future will these promising clues work? next step is to test these drugs in human trials The researchers have already begun this process, and through these trials, they will examine important factors in the context of COVID-19, such as dosage, toxicity, and potentially beneficial or harmful interactions (biovalleybioon.com) References: 1, Scientists test 47 old drugs against the coronavirus Results hadd show leads
2, African green monkey (Vero) cells provide an alternative home cell system for influenza A and B viruses.
3: PharmaMar Has Announced The Spanish MedicineS Agency Has Authorized the APLICOV-PC Clinical Trial With Aplidin? (Plitidepsin) for the patient sings with COVID-19
4, Effect of Dememerthorphan, Diphenhydra, and Placebo on Nocturnal Cough and Sleep Quality for Coughing Children and Their Parents 5
NIH clinical trial of hydroxyquine, a potential therapy for COVID-19, a ters Comparative efficonacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV
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, Haloperidol
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A SARS-CoV-2 protein interaction map map reveals targets for drug repurposing Nature (2020) https://doi.org/10.1038/s41586-020-2286-9
9: SARS-CoV-2 VIRUS HUMAN HUMAN PROTEIN-PROTEIN INTERACTION MAP