COVID-19 Research From Norway and Estonia Shows Limitations Of Plasma Therapy and Also Identifies Six New Antivirals Candidates And A New Drug Combo
: A new research led by Norwegian University of Science and Technology involving both Norwegian and Estonian researchers have established a cell culture that allows them to test antibody-laden plasma, drugs and drug combinations in the laboratory. The team also identified six potential antiviral candidates out of a base of 136 already approved drugs that could be repurposed. One combination of two drugs was so effective that the researchers hope others can begin clinical trials on the drugs immediately.
The research team identified six existing safe-in-humans broad-spectrum antivirals that worked against the disease in laboratory tests. The six drugs were nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine, said Dr Denis Kainov, an associate professor at the university's Department of Clinical and Molecular Medicine, and senior author of the research paper.
Significantly two of the six, when combined, showed an even stronger effect in infected cell cultures.
Dr Kainov told Thailand Medical News, "This orally available drug combination: nelfinavir and amodiaquine inhibits the virus infection in cell cultures. It should be tested further in pre-clinical studies and clinical trials now."
Dr Magnar Bjørås, a Professor in the Norwegian University of Science and Technology's (NTNU) Department of Clinical and Molecular Medicine, and one of the paper's co-authors said, "This is exciting new data from the work we did."
However the research also uncovered some bad news is that another, non-drug treatment ie the use of antibody-laden plasma from recovered patients to treat the severely ill may only work if the donor has recently recovered from COVID-19.
Dr Svein Arne Nordbø, an Associate Professor at the university's Department of Clinical and Molecular Medicine and an MD at Department of Medical Microbiology at St. Olavs Hospital in Trondheim, and another of the paper's authors explained, "This means if you collect blood from patients who have recovered from COVID-19 after two months from diagnosis of the disease, and transfuse their plasma/serum to severely sick patients, it may not help,"
The research findings have been published in the journal Viruses
The team developed a cell culture that they could use to grow SARS-CoV-2, the name of the coronavirus that causes COVID-19. The culture allowed them to actually test the efficacy of the different drugs in the laboratory. They determined that a cell type called Vero-E6 was best suited to propagate the coronavirus, and were able to screen 136 drugs using the cell culture.
The study team also wanted to look more closely at the efficacy of using blood plasma from recovered patients to treat people with COVID-19. The new Vero-E6 cell line enabled them to develop a "neutralizing antibody" test, which they could use to determine the strength of antibodies from the blood of recovered patients.
e team took blood plasma from recovered patients and added it to the cell cultures containing the live virus. That allowed them to see how effectively the antibodies in the plasma neutralized or killed the virus that was growing in the cell culture.
Dr Nordbø points out that the only way to know if the convalescent plasma is strong enough is by adding dilutions of it to a live virus strain and testing the mixtures on cell lines that can propagate the virus, as the researchers did.
It must be noted that ordinary antibody tests may not reflect the ability of the convalescent plasma to actually kill or neutralize the virus, he said. That means the neutralization tests are still the most specific.
The study showed that antibody effectiveness declined with time
Interestingly the neutralizing antibody tests allowed the researchers to test convalescent sera from a number of recovered patients. They were able to see that some recovered patients didn't produce lots of antibodies at all, a finding that has been confirmed by other research.
Most Importantly they also were able to see that the more recent the recovery from COVID-19, the more effective was the serum. Two months after a patient had been diagnosed, their serum didn't have enough antibodies to combat the virus in the cell culture.
Dr Nordbø stressed, "The conclusion so far is that clinicians need to collect plasma for treatment purposes as soon as patients recover from COVID-19, because the amounts of antibodies decline with time.”
Dr Mona Høysæter Fenstad, a researcher at the Department of Immunology and Transfusion Medicine at St. Olavs Hospital, and another co-author said that this finding however is not contrary to the notion of lasting immunity. If the patient was exposed the virus a second time, the cells of the immune system would most likely be prepared to increase the production of antibodies again,
The research team hopes that other international researchers would take note of the limitations of convalescent plasma therapy and also start clinical research on the six identified antivirals especially the drug combo.
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