• New 47 Known Drugs That Can Fight Covid-19 discovered by a group of scientists from the University of California, San Francisco


    • Instead of thinking about new-designed drugs, a group of scientists from the University of California, San Francisco searched among the 2,000 drugs already approved for humans for some that could treat or indicate a therapeutic pathway for COVID-19.

Using a map of SARS-CoV-2 proteins that bind to humans, the scientists reviewed the list of 2,000 FDA-approved drugs for options.
A coronavirus map – that was what could help find the weak spots through which to attack the new pathogen. “The more we know how human cells bind, invade, and hijack , the more effective the drug search will be to combat it, ” said Nevan Krogan, director of the Institute for Quantitative Bioscience at the Gladstone Institute and colleagues at the University of California in San Francisco ( UCSF ).

“The map shows all the coronavirus proteins and all the proteins in the human body that were found to interact with them,” he explained in The Conversation . “In theory, any intersection between viral proteins and human proteins on that map is a place where a drug could fight SARS-CoV-2 . But instead of trying to develop new drugs, “the researchers distinguished themselves,” we look at the more than 2,000 unique substances already approved by the Food and Drug Administration ( FDA ). ”

Somewhere in such a broad catalog , they speculated, “there could be a few drugs or components that interact with the same human proteins as the coronavirus,” Krogan said. “And we were right.”

The UCSF multidisciplinary team identified 69 drugs and components with potential to treat COVID-19 . As he did so, he sent samples of these substances to the Pasteur Institute in Paris and the Mount Sinai Icahn School of Medicine in New York for testing. So far, 47 showed “strong guidelines for treatment” and ” two separate mechanisms ” were identified on how they would intercept SARS-CoV-2, as synthesized in a first study .

In principle, these guidelines and mechanisms derived from the crossing between the coronavirus map and the FDA catalog indicated only potential interactions : “We did not know if the drugs we identified would make a person more resistant to the virus or more susceptible , if they would do something or nothing ”. For this, it was necessary to test them in live samples of the cause of COVID-19 and in cells, which were taken from the green monkey because they react in a very similar way to humans.

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“After infecting these monkey cells with the live virus, our colleagues in Paris and New York added the drugs we identified to half of them, and kept the other half as controls,” the microbiologist detailed in his article. “Then they measured the amount of virus in the samples and the number of cells that were still alive . If the samples had lower virus content and higher live cell content than the control group, that suggested they interfered with viral multiplication . ”

The trials included some of the possible combinations and gave all kinds of results: “Some drugs were used to fight the coronavirus, while others made the cells more susceptible to infection .” But overall, the most revealing conclusions were two, Krogan noted: “We found individual drugs that seem promising to fight the coronavirus (or that can make people more susceptible to it)” and ” we know, at the cellular level, from why does that happen ”.

The UCSF researchers mainly identified two groups of substances that affect the virus in two different ways, one of which had not been described before .

The first group interrupts the translation of the RNA message , which is one of the final steps that the coronavirus takes to multiply . When it enters a cell, SARS-CoV-2 appropriates its natural mechanisms to make copies of itself. First it replicates , then it transcribes the instructions to do that numerous times thanks to the cell’s own capacity and finally it translates that message : at this point the proteins make new copies that go on to infect other cells . And the process begins again.

“In reviewing the map, we noted that various viral proteins interacted with human proteins involved in translation and a number of drugs interacted with these proteins. After testing them, we found two compounds that interrupt the translation of the virus, ”announced the expert.

Currently they are used to treat multiple myeloma: they are ternatin-4 and zotatifin . “They appear to fight COVID-19 by binding to and inhibiting the proteins the cell needs to translate.”

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A molecule similar to ternatin-4, the drug Aplidin , is currently under study , an antitumor of Spanish origin whose active ingredient is plitidespine . According to said Luis Mora, director of the company that produces it , PharmaMar , its effects against COVID-19 could be ” a thousand times higher than those getting remdesivir” antiviral of Gilead approved by the FDA.

Instead, zotatifine targets another protein. The UCSF research team is currently working with the laboratory that produces it, eFFECTOR Therapeutics , to begin clinical trials as soon as possible . As explained by the executive director of the firm, Steve Worland, unlike the other antivirals, this molecule, originally created against cancer , does not target the virus but acts on the cells that SARS-CoV-2 hijacks .

“The second group of drugs that we identified works completely differently,” Krogan continued. It works on the sigma receptors , a protein present in many tissues of the human body, with great concentration in the nervous system , for which it is associated with addictive behaviors, personality disorders and depression , but it has also been identified in cardiovascular function and cancer .

Cellular receptors, found both on the inside and on the surface of cells, “act as specialized switches ,” the researcher compared: “When a specific molecule binds to a specific receptor, it thus signals the cell to do a specific task . Viruses often use receptors to infect cells. ”

The original map had shown that two important receptors in pharmacological treatments, SigmaR1 and SigmaR2 , could participate in the fight against COVID-19. “The tests confirmed our suspicions,” Krogan continued.

Seven drugs or molecules that interact with these receptors were identified in the laboratories : “Two antipsychotics, haloperidol and melperone , which are used to treat schizophrenia , showed antiviral activity against SARS-CoV-2. Two powerful antihistamines, clemastine (or meclastine) and chloperastine, also showed antiviral activity, as did compound PB28 (a piperazine derivative) and the female hormone progesterone . ”

Although the mechanism the coronavirus employs is not exactly known, its proteins are believed to manipulate these switches to help produce copies of itself . Therefore, reducing the activity of these receptors would probably limit the multiplication of the microorganism.