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Developing a multi-drug cocktail against COVID-19

A new study has identified 21 existing drugs that stop the replication of SARS-CoV-2, the virus that causes COVID-19. Scientists analyzed one of the world’s largest collections of known drugs for their ability to block the replication of SARS-CoV-2. They identified 100 molecules with confirmed antiviral activity in laboratory tests. Of these, 21 drugs were determined to be effective at concentrations that could be safely achieved in patients. Notably, four of these compounds were found to work synergistically with remdesivir, a current standard-of-care treatment for COVID-19.

“Remdesivir has proven successful at shortening the recovery time for patients in the hospital, but the drug doesn’t work for everyone who receives it. That’s not good enough,” said study investigator Sumit Chanda, said who is the director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys, La Jolla, California. “As infection rates continue to rise in America and around the world, the urgency remains to find affordable, effective and readily available drugs that can complement the use of remdesivir, as well as drugs that could be given prophylactically or at the first sign of infection on an outpatient basis.”

In the study, the research team performed extensive testing and validation studies, including evaluating the drugs on human lung biopsies that were infected with the virus. Among 21 drugs that were effective at blocking viral replication, the scientists found that 13 have previously entered clinical trials for other indications and two are already FDA approved: astemizole (allergies), clofazamine (leprosy). Remdesivir has received Emergency Use Authorization from the FDA for treating COVID-19. The researchers found that four of the drugs worked synergistically with remdesivir, including the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug that has reached Phase 3 clinical trials.

How is the virus mutating?

The SARS-CoV-2 mutation rate currently is remaining low. Across Europe and Italy, the most widespread strain is G, while the L strain from Wuhan is gradually disappearing. These mutations, however, do not impinge on the process of developing effective vaccines. It is now known that the virus causing the COVID-19 pandemic presents in the form of at least six strains. Despite its mutations, the virus shows little variability, and this is good news for the researchers working on a viable vaccine.

Italian Researchers at the University of Bologna analyzed 48,635 coronavirus genomes, which were isolated by researchers in labs all over the world. It was then possible for researchers to map the spread and the mutations of the virus during its journey to all continents. Their study was published in the journal Frontiers in Microbiology.

The results are encouraging at this time. The coronavirus presents little variability, approximately seven mutations per sample. Common influenza has a variability rate that is significantly higher. “The SARS-CoV-2 coronavirus is presumably already optimized to affect human beings, and this explains its low evolutionary change,” said study coordinator Federico Giorgi, who is in the Department of Pharmacy and Biotechnology at the University of Bologna in Italy. “This means that the treatments we are developing, including a vaccine, might be effective against all the virus strains.”

The original strain is the L strain, which appeared in Wuhan in December 2019. Its first mutation was the S strain and it appeared at the beginning of 2020. Since mid-January 2020, researchers identified strains V and G, and strain G is the most widespread. It mutated into strains GR and GH at the end of February 2020. “Strain G and its related strains GR and GH are by far the most widespread, representing 74% of all gene sequences we analyzed,” said Giorgi. “They present four mutations, two of which are able to change the sequence of the RNA polymerase and Spike proteins of the virus. This characteristic probably facilitates the spread of the virus.”

Currently, strains G and GR are the most frequent across Europe and Italy. The GH strain seems close to non-existence in Italy, while it occurs more frequently in France and Germany. This seems to confirm the effectiveness of previous containment methods. In North America, the most widespread strain is GH, while in South America the GR strain is more frequent.

Lung ultrasound testing may be valuable tool

A new study found that lung ultrasound testing is highly sensitive for detecting abnormalities in patients with COVID-19. In addition, ultrasound testing may be useful for diagnosing both the infection duration and disease severity.

From March 3 to March 30, 2020, researchers performed lung ultrasound testing on consecutive patients with positive reverse transcriptase polymerase chain reaction (RTPCR) test results for SARS-CoV-2. They compared the percentages of patients with each ultrasound finding between groups with different symptom durations and disease severity.

All 28 patients (14 men and 14 women; age range, 21 to 92 years) had positive findings on both lung ultrasound and chest CT scan. On ultrasound tests, B-lines were present in 100% of patients, and 19 (67.9%) patients had pulmonary consolidation. Thickened pleural lines were observed in 17 patients (60.7%), and only one patient (3.6%) showed a small amount of pleural effusion. These findings can help guide physicians on how best to treat an individual. In addition, these new findings are very important because ultrasound tests can be performed with bedside portable systems to further protect health care workers.

John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute. He can be reached at medicalminutes@gmail.com.

Author Bio

John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute.

• Email: medicalminutes@gmail.com