As the world struggles to adjust to a new normal with the novel coronavirus, researchers around the globe are working to end the pandemic. In Japan, AMED is supporting scientists to contribute to the international effort to develop a vaccine, as well as drugs to treat COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
False-color transmission electron micrograph of a SARS-CoV-2 coronavirus particle isolated from a COVID-19 patient in the United Kingdom. (c) NATIONAL INFECTION SERVICE/SCIENCE PHOTO LIBRARY
Quest for a vaccine
The most eagerly awaited defence against the coronavirus is a vaccine. Around the world, countries have pledged billions of dollars to support vaccine research and implementation, and there are more than 70 candidates in development. In May, Osaka-based pharmaceutical company Shionogi & Co. said it hopes to begin clinical trials this year with an eye to launching a vaccine as early as autumn 2021. It’s aiming to produce enough vaccine for 10 million people, and is working with its subsidiary, Yokohama-based manufacturer, UMN Pharma, and researchers at Japan’s National Institute of Infectious Diseases (NIID).
The studies are funded from the budget of the Japan Agency for Medical Research and Development (AMED), created through the Japanese government in 2015 for the progression of medical studies.
The main component of the NIID vaccine candidate, known as an antigen, is a protein molecule that triggers an expressed immune reaction to the COVID-19 virus. To do this, an approach known as the baculovirus expression vector (BEVS) formula is created.
“BEVS products have already been used in the human papillomavirus vaccine and the HA influenza vaccine,” says Hideki Hasegawa, director of the NIID Influenza Virus Research Center and principal investigator of the project. “From our experience with influenza vaccine studies, we know that serum IgG antibodies do not protect against viral infection in upper respiratory epithelial cells. IgA secretory antibodies, on the other hand, play an essential role in preventing respiratory tract infections. Our ultimate goal is a COVID-19 mucosal vaccine that induces protective secretory IgA antibodies in the respiratory tract mucosa.
Like many vaccines, the NIID candidate also includes a molecule called adjuvant, whose goal is to stimulate the immune reaction and reduce the amount of antigen needed. The team plans to use TLR9 or TLR3 agonists as adjuvants, according to Hasegawa, who is also involved with Kyushu University as well as Florida-based AIM Immuno Tech for adjuvant candidates.
Work at NIID is progressing despite the requirement to test for the virus in biosafety point 3 facilities, which require protective clothing and devices, such as biosafety cabinets. There are also limits on physical gatherings with colleagues, although social restrictions are not as strict. in Japan as in some countries.
A multifront fight
AMED is supporting drug discovery efforts by adding a randomized, open-label clinical trial to compare favipiravir, a drug developed by Fujifilm Toyama Chemical Co. , a unit of Fujifilm Holdings, for the treatment of influenza. It was expected that favipiravir, advertised as Avigan, could help only in moderate and mild cases of COVID-19.
With AMED, NIID researchers also searched for compounds that could inhibit the spread of the virus using strategies such as random screening of libraries of existing approved drugs. They also focus on antibodies.
“Using a high-throughput monoclonal antibody isolation technique, a human-like curative monoclonal antibody opposite the virus is temporarily established,” said Makoto Takeda, chair of NIID’s Department of Virology 3 and principal investigator of the project. “We are currently working on the study of the mechanisms of infection; purification and structural studies of proteins of maximum purity; selection of libraries of small molecule compounds; preparation of recombinant antigens targeting curative antibodies; studies and progression of human monoclonal antibodies and those antigens; detection of existing medications; virus spread, progression of real-time oppositely transcripted polymerase chain reaction formulations for surveillance formulas; and selection of libraries of herbal compounds.
One such herbal compound has shown its potential. Cepharanthin, an anti-inflammatory from the perennial vine Stephania cephalantha Hayata, has been used in Japan for decades to treat disorders such as low mobile white blood cell count, dry mouth and alopecia. In a paper posted on BioRxiv, a repository of preprints of studies that have not been peer-reviewed, Takeda and his colleagues describe how they developed a SARS-CoV-2 isolation and propagation formula that helped create a detection formula. effective for antiviral medications. Computer models showed that a drug called nelfinavir can simply inhibit viral replication, while cepharanthin can prevent the virus from attaching to and entering mobile phones. In vitro tests have demonstrated its synergistic effect against the virus. “The nelfinavir/cefaranthin mixture demonstrated its predicted efficacy in controlling viral proliferation, both in disease progression and transmission risk,” the authors wrote.
Defeating the coronavirus is a gigantic effort. As he looks for other potential teams to contribute to this effort, Takeda is encouraged that Japan has yet to contribute.
“Of course, Japan would also possibly face the threat of an explosion of cases, like in the United States or Europe,” he says, “but our wisdom about COVID-19 is greater than before, and each and every one of us today will be informed “. more about what we do to engage the virus. COVID-19. “
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