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Landmark Discovery May Lead to Safe, Effective Antiviral Drugs Against COVID-19

AHA Publisher — Fri, 09 Apr 2021 07:00:03 +0000

Argonne National Laboratory via News-Medical – The COVID-19 vaccines currently rolling out are providing hope that the spread of the disease can be halted. But infection rates are still high, and for those who contract COVID-19, the search for effective treatments remains important. Researchers examining the atomic structure of SARS-CoV-2, the virus that causes COVID-19, have made a landmark discovery that could contribute critical information to the design of safe and effective antiviral drugs in the fight against the virus. “Understanding enzymes goes hand in hand with understanding their atomic structures -; and the higher resolution the better, because subtle differences can affect the interpretation. We wanted the best data possible, so we went to the APS.” (Natalie Strynadka, University of British Columbia) Using a powerful X-ray beam to study SARS-CoV-2 proteins in crystallized form, a team from the University of British Columbia (UBC) has observed -; for the first time ever -; the virus’s main protease, an important enzyme of the virus, performing its function. This widely pursued antiviral target is a central enzyme that allows the virus to cut up large proteins called polyproteins into smaller functional units, a process necessary for the virus to be replicated and infect other human cells. “What we’ve captured at high resolution is one of the important steps in that process that has never been visualized before in any viral protease of this class,” said Natalie Strynadka, the UBC biochemistry professor who led the research team with colleague Mark Paetzel. The research was published in Nature. The breakthrough was made possible by the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory. The APS produces X-rays that are roughly a billion times brighter than those used by doctors and dentists, allowing researchers to examine the structure of the coronavirus protease in very fine detail at the atomic level. Data was captured at the General Medical Sciences and Cancer Institutes Structural Biology Facility at beamline 23-ID-B at the APS. The newly uncovered information may be of particular interest to scientists worldwide who are racing to develop antiviral treatments for COVID-19. If the main protease is inhibited by a small molecule drug, the polyproteins won’t be clipped into functional pieces, effectively blocking viral replication and subsequent transmission. “We now have a much better blueprint of these mechanistic structures that will inform making the best inhibitor possible,” Strynadka said. ”Better knowing the structure as we now do helps guide drug research, narrowing the field of potential targets instead of having to screen billions of potential molecules.” Michael Becker, a protein crystallographer with Argonne’s X-ray Science Division, said Strynadka’s research stands out because the team was focused on understanding the mechanism of the protease. “This understanding will improve everyone else’s work in designing drugs,” Becker said. ”Because the more deeply you understand how something works, the better the chance you have of controlling or stopping it.” Remote access capabilities at Argonne made it possible for the researchers in British Columbia to collect data in real time and to manipulate the APS beamline located about 2,200 miles away in Illinois. UBC team members Jaeyong Lee and Liam Worrall shipped crystals of the SARS-CoV-2 main protease preserved in liquid nitrogen from Canada to Argonne. Workers at the APS were on hand to answer questions, ensure the working order of the equipment, and load the samples. “The remote interface is fantastic. It’s almost like being there,” Strynadka said. ”We’re very thankful for the use of the APS. Canada does have a national synchrotron facility, but it currently doesn’t have the same capability as the APS, which is a very high-level facility with micro-focused beams. Understanding enzymes goes hand in hand with understanding their atomic structures -; and the higher resolution the better, because subtle differences can affect the interpretation. We wanted the best data possible, so we went to the APS.” To read the original article click here.

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Israel to Begin Clinical Trials of Covid-19 Vaccine

AHA Publisher — Tue, 27 Oct 2020 07:00:19 +0000

Abigail Klein Leichman via Israel21c – The governmental Israel Institute for Biological Research (IIBR) has approval from the Ministry of Health and the Helsinki Committee to begin testing its vaccine, BriLife, against the SARS-CoV-2 coronavirus on November 1. The IIBR has prepared 25,000 doses of BriLife and has recruited the first volunteers in an 80-person clinical trial, 40 at Hadassah University Medical Center in Jerusalem and 40 at Sheba Medical Center in Ramat Gan. Each volunteer, aged 18 to 55, will receive an injection (vaccine or placebo). After a few hours of supervision he/she will be discharged and monitored for three weeks for any possible side effects and for the development of antibodies to the virus in response to the vaccine. The second phase will include extensive safety tests on 960 healthy volunteers, to begin in December in several medical centers across Israel. In this phase, scientists aim to complete vaccine safety precautions, determine effective dosage, and further determine the vaccine’s effectiveness. The third and final phase is a large-scale trial to test the effectiveness of BriLife, with the participation of up to 30,000 volunteers. Subject to the success of the first two phases, this phase is scheduled to begin in April or May. If it is successful, the vaccine may be approved for mass use. On June 21, ISRAEL21c reported that a single dose of the IIBR’s recombinant VSV-∆G-spike vaccine “results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2” in Syrian golden hamsters in a successful preclinical trial. It was also tested successfully in mice, rabbits and pigs, paving the way to human trials. “Our final goal is 15 million doses for the residents of the State of Israel and for our close neighbors,” said Prof. Shmuel Shapira, director of the IIBR. The research institute in Ness Ziona, which is part of the Ministry of Defense, has been directing all its efforts in the past few months toward novel coronavirus research. In collaboration with several partners, the IIBR also is developing an antibody-based Covid-19 treatment and a new method to detect the virus through breath analysis. Shapira said the name BriLife puts together the Hebrew word for health, briut, with “il” for Israel and “life” — which speaks to the importance of the vaccine. To read the original article click here. For more articles from Israel21c click here.

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Study of 300 COVID-19 Patients Shows Efficacy of Convalescent Plasma Therapy

AHA Publisher — Fri, 14 Aug 2020 07:00:29 +0000

Elsevier via News-Medical Net – A preliminary analysis of an ongoing study of more than 300 COVID-19 patients treated with convalescent plasma therapy at Houston Methodist suggests the treatment is safe and effective. The results, which appear now in The American Journal of Pathology, represents one of the first peer-reviewed publications in the country assessing efficacy of convalescent plasma. From March 28, when Houston Methodist became the first academic medical center in the nation to infuse critically ill COVID-19 patients with plasma donated from recovered patients, research physicians have used the treatment on 350 patients. The study tracked severely ill COVID-19 patients admitted to Houston Methodist’s system of eight hospitals from March 28 through July 6. These latest results from Houston Methodist that now measured medical effectiveness offer valuable scientific evidence that transfusing critically ill COVID-19 patients with high antibody plasma early in their illness – within 72 hours after hospitalization proving most effective – reduced the mortality rate. The study, titled “Treatment of COVID-19 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality,” was led by principal investigator Eric Salazar, MD, PhD, assistant professor of Pathology and Genomic Medicine with the Houston Methodist Hospital and Research Institute, and corresponding author James M. Musser, MD, PhD, chair of the Department of Pathology and Genomic Medicine at Houston Methodist. “Our studies to date show the treatment is safe and, in a promising number of patients, effective. While convalescent plasma therapy remains experimental and we have more research to do and data to collect, we now have more evidence than ever that this century-old plasma therapy has merit, is safe, and can help reduce the death rate from this virus.” (Dr. James M. Musser, Chair of the Department of Pathology and Genomic Medicine at Houston Methodist) The research team found that those treated early in their illness with donated plasma that has the highest concentration of anti-COVID-19 antibodies are more likely to survive and recover than similar patients who were not treated with convalescent plasma. Patients with a history of severe reactions to blood transfusions, those with underlying uncompensated and untreatable end-stage disease, and patients with fluid overload or other conditions that would increase the risk of plasma transfusion were excluded. The patients were tracked for 28 days after plasma transfusion and compared to a control group of similar COVID-19 patients who did not receive convalescent plasma. An observational propensity score-matched analysis was used to balance the characteristics of participants and allow for an objective interpretation of the results at this stage. Several studies have measured safety, showing that the more than 34,000 COVID-19 patients in the United States who have received plasma transfusions for COVID-19 experienced minimal adverse effects. To read the original article click here.

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COVID Doc Says Hydroxychloroquine ‘Highly Effective’ and Fears Are Overblown – Now FDA Chief Admits It Might Help

AHA Publisher — Sat, 01 Aug 2020 07:00:10 +0000

Lori Johnson via CBN News – A Tennessee physician has a message for COVID-19 patients: Use hydroxychloroquine “if you can find a doctor with guts enough to prescribe it.” Meanwhile, the US Food and Drug Commissioner Stephen Hahn said some studies “suggest a benefit” to using the drug on COVID-19, despite the fact that the government agency issued guidance stating the use of the drug should be avoided unless it’s being studied in a clinical trial or for hospital use. In a radio interview, Hahn reiterated the fact that doctors are free to prescribe the drug “off label,” and that the FDA “does not regulate the practice of medicine.” Dr. Tom Rogers is one of those physicians who prescribe hydroxychloroquine to his COVID-19 patients. He told CBN News he personally has found the drug to be a “highly effective” way to treat the virus, provided the drug is prescribed in the early stages of the disease and is combined with the antibiotic azithromycin and a zinc supplement. “It’s a very controversial, kind of ‘Trump drug’,” he told CBN News. “There were initially a bunch of studies that said it worked, and then the powers that be came out with some other studies that said it didn’t work. But there are many, many studies and many doctors who I’ve talked to personally, on the front lines that use it all the time and it works.” He continued, “You have to use it very early,” he said. “The studies that said it didn’t work, those were hospitalized patients that were very sick.” He said possible negative consequences of taking hydroxychloroquine are over-blown. “They’re claiming it causes cardiac arrhythmia, which is rare,” he says. “I’ve never seen that. I’ve talked to rheumatologists who’ve used it for decades, they’ve never seen it.” Dr. Rogers says he prefers to prescribe the hydroxychloroquine cocktail to patients with symptoms such as fever, aches, loss of taste or smell, and believes it can prevent a patient from going to the hospital. In addition to hydroxychloroquine combined with azithromycin and zinc, Dr. Rogers said there are other ways patients in the early stages of COVID-19 can avoid landing in the hospital. Those include the inhaled steroid Budesonide combined with azithromycin and zinc. Budesonide is a common asthma drug he prescribes to patients who test positive for COVID-19 and have mild respiratory symptoms such as “cough, wheezing or shortness of breath that’s not acute yet.” Still, neither hydroxychloroquine nor budesonide is recommended by the FDA to treat COVID-19 because their effectiveness has not been proven in randomized, controlled studies, which is the standard requirement for FDA approval. To read the original article click here. For more articles from CBN News click here.

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New Hydroxychloroquine Study Proves Trump Right, Says It ‘Significantly’ Cuts Death Rate

AHA Publisher — Sun, 05 Jul 2020 07:00:40 +0000

Benjamin Gill via CBN News – A substantial new study has found that the anti-malaria drug hydroxychloroquine helped patients survive COVID-19. In fact, the study from the Henry Ford Health System in Michigan said the drug “significantly” cut the death rate of patients. “Treatment with hydroxychloroquine cut the death rate significantly in sick patients hospitalized with COVID-19 – and without heart-related side-effects,” the health organization reports. Their analysis of 2,500 COVID-19 patients found the drug can be effective if patients received it early in their treatment. “Our analysis shows that using hydroxychloroquine helped save lives,” said neurosurgeon Dr. Steven Kalkanis, CEO, Henry Ford Medical Group and Senior Vice President and Chief Academic Officer of Henry Ford Health System. “As doctors and scientists, we look to the data for insight. And the data here is clear that there was benefit to using the drug as a treatment for sick, hospitalized patients.” President Trump had touted the drug early on as a possible experimental treatment for virus patients, but then studies found conflicting results about its effectiveness and the news media hammered him on it. One of the earlier negative studies was later retracted. Scientists from the Henry Ford Health System explained why their study was successful. “The findings have been highly analyzed and peer-reviewed,” said Dr. Marcus Zervos, division head of Infectious Disease for Henry Ford Health System, who co-authored the study with Henry Ford epidemiologist Dr. Samia Arshad. “We attribute our findings that differ from other studies to early treatment, and part of a combination of interventions that were done in supportive care of patients, including careful cardiac monitoring. Our dosing also differed from other studies not showing a benefit of the drug. And other studies are either not peer-reviewed, have limited numbers of patients, different patient populations or other differences from our patients.” To read the original article click here. For more articles from CBN News click here.

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