Purdue says Wuhan virus genetically similar to SARS, works toward therapeutics
WEST LAFAYETTE, Ind.—Purdue University scientists Andrew Mesecar, who is the university’s Walther Professor in Cancer Structural Biology and head of the Department of Biochemistry, and Arun Ghosh, the Ian P. Rothwell Distinguished Professor of Chemistry, have been working to develop both oral medicines and vaccines to fight coronaviruses, and are now working to test their potential drug molecules on the new SARS-like Wuhan coronavirus.
Although no potential drug identified now will be helpful in the current outbreak, the researchers hope that they can use the discoveries they make with the current virus to better mitigate future outbreaks.
In the case of these Purdue scientists, they are developing a drug that works by blocking two of the coronavirus enzymes (proteases), thus preventing it from replicating. Moreover, this is not unlike what they have seen before, which may make things a little easier, with Mesecar noting, “The drug targets we’ve identified are over 95-percent identical to the enzyme targets we saw on the SARS virus.”
SARS, or severe acute respiratory syndrome, was first discovered in Asia in February 2003, and the outbreak lasted approximately six months as the disease spread to more than two dozen countries in North America, South America, Europe and Asia before it was stopped in July 2003. But technology and know-how has improved since then.
“In 2002 when the SARS outbreak happened, it took months to get to the point where we are now,” Mesecar said. “With this outbreak, scientists were able to isolate the virus and sequence the genome in less than two weeks. One week later, an additional 20 genomes were available. In another week or two, we’ll be able to begin to see if the virus is mutating.”
In identifying drug targets on the coronavirus, they take an antiviral approach similar to what Ghosh used to develop the anti-HIV drug darunavir, which is sold under the brand name Prezista.
“MERS virus and the SARS virus are more different genetically,” Mesecar explains. “But the Wuhan virus is genetically almost identical to the SARS virus and, therefore, it is expected to look and act nearly the same.”
However, the future of a drug like this is uncertain, given that the intermittent nature of these kinds of outbreaks and the relatively small market for the drug compared to those who suffer from chronic diseases means pharma companies have less incentive to develop the drugs.
Mesecar is working to set up a rapid-response system of scientists that could quickly develop drugs during future outbreaks caused by genetic variants of the coronavirus. The goal is to have a library of FDA-approved or almost-approved compounds that have been predetermined to work on specific coronaviruses so that when an outbreak appears, medicines can be produced and distributed quickly.
Adapted from a Purdue University article online by Steve Tally
Moderna gets funding for mRNA vaccine against novel coronavirus
CAMBRIDGE, Mass.—Moderna Inc., a clinical-stage biotechnology company focused on messenger RNA (mRNA) therapeutics and vaccines, and the Coalition for Epidemic Preparedness Innovations (CEPI), recently announced a new collaboration to develop an mRNA vaccine against the novel coronavirus (2019-nCoV) that seems to have originated in Wuhan, China.
Under the terms of the agreement, Moderna will manufacture an mRNA vaccine against 2019-nCoV, which will be funded by CEPI. The Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), collaborated with Moderna to design the vaccine. NIAID will conduct IND-enabling studies and a Phase 1 clinical study in the United States.
Over the past four years Moderna has had six positive Phase 1 clinical readouts in its prophylactic vaccines modality and moved two additional programs into development. Moderna’s technology platform, fully integrated manufacturing site and development experience, combined with a multi-year relationship with the NIH, including exploring ways to respond to public health threats, allows for the rapid identification and advancement of a vaccine candidate against 2019-nCoV.
“Moderna’s commitment to global public health is aligned with CEPI’s vision of creating a world in which epidemics are no longer a threat to humanity,” said Dr. Richard Hatchett, CEO of CEPI. “We are pleased with the pace of our combined response to the emerging threat of the novel coronavirus. Through our partnership with Moderna and the NIH, we hope to speed the development of a vaccine against the coronavirus and help to alleviate the burden of disease.”
Added Stéphane Bancel, CEO of Moderna: “We believe our mRNA vaccine technology offers potential advantages in the speed of development and production scalability, which positions Moderna to potentially develop a vaccine against coronavirus, 2019-nCoV. Advances in global public health require the collective effort of public-private partnerships—no organization can act alone. We are honored to be supporting NIH and CEPI in their mission to identify a potential vaccine to prevent infection. It is impressive that CEPI was able to commit to this grant in a matter of days. We are thankful for the financial support from CEPI and the multi-year scientific collaboration we have with the NIH.”
Australia grows coronavirus in the lab
MELBOURNE, Australia—Scientists from the Peter Doherty Institute for Infection and Immunity, a joint venture between the University of Melbourne and the Royal Melbourne hospital, have successfully grown the Wuhan coronavirus from a patient sample, which will provide expert international laboratories with crucial information to help combat the virus.
This reportedly represented the first time the virus had been grown in cell culture outside of China.
The Royal Melbourne Hospital’s Dr. Julian Druce, head of the Virus Identification Laboratory at the Doherty Institute, said this was a significant breakthrough as it will allow accurate investigation and diagnosis of the virus globally.
“Chinese officials released the genome sequence of this novel coronavirus, which is helpful for diagnosis, however, having the real virus means we now have the ability to actually validate and verify all test methods, and compare their sensitivities and specificities—it will be a game-changer for diagnosis,” Druce said. “The virus will be used as positive control material for the Australian network of public health laboratories, and also shipped to expert laboratories working closely with the World Health Organization in Europe.”
Doherty Institute Deputy Director Dr. Mike Catton said that possession of a virus isolate extended what could be achieved with molecular technology in the fight against this virus.
The Doherty Institute-grown virus is expected to be used to generate an antibody test, which allows detection of the virus in patients who haven’t displayed symptoms and were therefore unaware they had the virus.
“An antibody test will enable us to retrospectively test suspected patients so we can gather a more accurate picture of how widespread the virus is, and consequently, among other things, the true mortality rate,” said Catton. “It will also assist in the assessment of effectiveness of trial vaccines.”
Alpha Genesis joins coronavirus battle
YEMASSEE, S.C.—On Feb. 3, the Alpha Genesis Primate Research Center said it is “utilizing its considerable resources to develop a much-needed vaccine to battle what looks to be an emerging pandemic” with regard to the Wuhan coronavirus.
One factor that potentially complicates the coronavirus battle is the limited availability of research primates necessary for vaccine development within the United States, according to the center, noting that U.S. scientists are almost entirely dependent upon China as a source of research monkeys, which were in critically short supply even prior to the recent viral outbreak. Now, these scientists face an even greater challenge as the supply of Chinese-sourced primates has been suspended indefinitely due to fears of further spreading the deadly disease.
Alpha Genesis indicates that it is putting its resources toward alleviating this problem and, according to Dr. Greg Westergaard, Alpha Genesis president and CEO, “The coronavirus threat is very serious, and the danger to the public quite real. Rapidly deploying the necessary resources to combat this outbreak will save lives, and prevent further human suffering.”
Coronavirus genome sequencing finds distinct genetic differences from 2003 SARS virus
NEW YORK—Although there are reportedly many similarities between the novel Wuhan coronavirus and the severe acute respiratory syndrome (SARS) virus that emerged some 17 years ago, researchers at the Chinese Center for Disease Control and Prevention and their collaborators have sequenced this newer coronavirus (2019-nCoV) pathogen from patient samples and have found it to be genetically distinct from SARS—as well as from the Middle East respiratory syndrome (MERS) virus that emerged in 2012.
As they described recently in The Lancet, the researchers sequenced samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan, China. In all, they developed ten genome sequences of 2019-nCoV from the nine patients, eight of which were complete. They then performed a phylogenetic analysis of the 2019-nCoV genomes and other coronavirus genomes to determine the evolutionary history of the new virus and to help infer its likely origin.
“Notably, 2019-nCoV was closely related (with 88 percent identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79 percent) and MERS-CoV (about 50 percent),” the authors wrote. “Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives, bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV.”