By Katherine Seley-Radtke, professor, Chemistry and Biochemistry, UMBC

The big idea

A paper came out in Nature on July 22 that further underscores earlier studies that show that neither the malaria drug hydroxychloroquine nor chloroquine prevents SARS-CoV-2 – the virus that causes COVID-19 – from replicating in lung cells.

Most Americans probably remember that hydroxychloroquine became the focus of numerous clinical trials following the president’s statement that it could be a “game changer.” At the time, he appeared to base this statement on anecdotal stories, as well as a few early and very limited studies that hydroxychloroquine seemed to help patients with COVID-19 recover.

Many in the antiviral field, including myself, questioned the validity of both, and in fact, one of the papers was later disparaged by the scientific society and the editor of the journal that published it.

Since then, HQC has had a bumpy ride. It was initially approved by the FDA for emergency use. The FDA then quickly reversed its decision when numerous reports of deaths caused by heart arrhythmias emerged. That news brought many clinical trials to a halt. Regardless, some scientists continued to study it in hopes of finding a cure for this deadly virus.

How the work was done

The new study was carried out by scientists in Germany who tested HCQ on a collection of different cell types to figure out why this drug doesn’t prevent the virus from infecting humans.

Their findings clearly show that that HQC can block the coronavirus from infecting kidney cells from the African green monkey. But it does not inhibit the virus in human lung cells – the primary site of infection for the SARS-CoV-2 virus.

In order for the virus to enter a cell, it can do so by two mechanisms – one, when the SARS-CoV-2 spike protein attaches to the ACE2 receptor and inserts its genetic material into the cell. In the second mechanism, the virus is absorbed into some special compartments in cells called endosomes.

Depending on the cell type, some, like kidney cells, need an enzyme called cathepsin L for the virus to successfully infect them. In lung cells, however, an enzyme called TMPRSS2 (on the cell surface) is necessary. Cathepsin L requires an acidic environment to function and allow the virus to infect the cell, while TMPRSS2 does not.

In the green monkey kidney cells, both hydroxychloroquine and chloroquine decrease the acidity, which then disables the cathepsin L enzyme, blocking the virus from infecting the monkey cells. In human lung cells, which have very low levels of cathepsin L enzyme, the virus uses the enzyme TMPRSS2 to enter the cell. But because that enzyme is not controlled by acidity, neither HCQ and CQ can block the SARS-CoV-2 from infecting the lungs or stop the virus from replicating.

Why it matters

This matters for several reasons. One, much time and money has been spent studying a drug that many scientists said from the very beginning was not going to be effective in killing the virus.

The second reason is that the studies that have reported antiviral activity for hydroxychloroquine were not in epithelial lung cells. Thus, their results are not relevant to properly studying SARS-CoV-2 infections in humans.

What’s next?

As scientists proceed with investigating new drugs as well as trying to repurpose old ones, like hydroxychloroquine, it is critical that researchers take the time to think about their study design.

In short, those of us involved in antiviral drug development should all take a lesson from this study. It is important not only to focus our efforts on pursuing drugs that will directly shut down viral replication, but also to study the virus in the primary site of infection.

*****

Katherine Seley-Radtke, Professor of Chemistry and Biochemistry and President-Elect of the International Society for Antiviral Research, University of Maryland, Baltimore County

This article is republished from The Conversation under a Creative Commons license. Read the original article.

[Deep knowledge, daily. Sign up for The Conversation’s newsletter.]

Header image: Chloroquine is an antimalarial drug originally developed in 1934; it doesn’t block coronavirus infection in humans. Brasil2 / Getty Images

UMBC’s Constantine Vaporis, professor of history, has partnered with TED-Ed Animations to produce A Day In The Life of A Teenage Samurai. This original video draws from over thirty years of scholarship Vaporis has completed on Japanese history and culture. The video is part of TED’s award-winning youth education program whose mission is to “amplify and capture the work of the world’s greatest teachers.” It currently has over 550,000 views.

The life of a samurai

“The creative process for the video required about eight months and involved me as the writer and educator in collaboration with a large creative and technical team,” shares Vaporis, the first UMBC history professor to have his research animated. “It was crafted in a style that is meant to be engaging to young viewers, historically truthful, but not photorealistic.” 

The video is set in Kôchi, Japan in 1800. It is a brief window into the fictional life of 16-year-old Mori Banshirô, a samurai in training who aspires to be an artist. Banshirô’s journey takes place during the Edo period (1603 – 1868), which is the focus of Vaporis’s research. 

During this time, samurai also served as government officials, teachers, masters of the tea ceremony, and artists. In his latest book, Samurai. An Encyclopedia of Japan’s Cultured Warriors (ABC/CLIO, 2019), Vaporis explores the life, practice, and history of these warriors.

Vaporis continues to partner with TED-Ed. TED-Ed has invited him to be a regular collaborator on future videos about Japan. He has already critiqued two other animations.

Decades researching Japanese history

In addition to his appointment in history, Vaporis has also served as the founding director of UMBC’s Asian studies program and is an affiliate professor of gender, women’s, and sexuality studies. This year he is one of forty scholars selected from around the world as a 2020 – 2021 fellow in residence in the School of Historical Studies at the Institute for Advanced Study in Princeton, NJ. During his fellowship Vaporis will work on his sixth book, Sword and Brush: Portraits of Samurai in Early Modern Japan.

Funding for Vaporis’s early research in Japan was through a Fulbright Scholars Award and a National Endowment for the Humanities Fellowship for College Teachers. He lived in Japan for seven years, completing archival research through these and additional fellowships.

This led to the books Breaking Barriers: Travel and the State in Early Modern Japan (Harvard University Press, 1995); Tour of Duty: Samurai, Military Service in Edo and the Culture of Early Modern Japan (University of Hawai’i Press, 2009); Nihonjin to sankin kôtai [The Japanese and Alternate Attendance] (Kashiwa shobô, 2010); and Voices of Early Modern Japan: Contemporary Accounts of Daily Life During the Age of the Shoguns (ABC/CLIO, 2012; Routledge, 2014, 2020).

Banner image: Constantine Vaporis at UMBC. Photo by Marlayna Demond ’11 for UMBC.

Gloria Chuku, chair andprofessor of Africana studies, has been named UMBC’s Lipitz Professor of the College of Arts, Humanities, and Social Sciences (CAHSS) for 2020 – 21. This distinguished professorship, funded by Roger C. Lipitz and the Lipitz Family Foundation, recognizes and supports innovative teaching and research. During her professorship, Chuku will carry out research for her new book project, Becoming Igbo in Nigeria and the Diaspora: A History of Ethnic Identity Formation and Negotiation. 

“I am humbled and grateful for my colleagues’ recognition of my contributions to the Africana studies department, CAHSS, and UMBC; to my profession; and to the fields of Igbo and Nigerian histories, African studies, and gender studies,” shares Chuku. “I feel validated.”

In the span of thirty years, Chuku’s internationally-renowned scholarship and teaching has explored the topics of ethno-nationalism, gender, economics, decolonization, conflict, and African-centered epistemological traditions of the Igbo people, the third largest ethnic group in Nigeria. 

Scholarship on Igbo culture

Chuku will spend time studying the Commonwealth and African manuscripts at Oxford University’s Bodleian Libraries in the coming year. She will also do archival research at The National Archives in London. Chuku will then return to the United States to review the unpublished papers on the Igbo people at the Melville J. Herskovits Library of African Studies at Northwestern University. 

This research will inform the writing of Chuku’s second book, about the processes of Igbo ethnic identity formation, negotiation, and integration across time. This includes Igbo identity within Nigeria and the global diaspora.

Chuku’s first book, Igbo Women and Economic Transformation in Southeastern Nigeria, 1900 – 1960 (Routledge, 2005), remains the most comprehensive study on Igbo women, covering all Igbo subculture zones. As a result of her work she was the first woman to receive the prestigious Ali Mazrui Award for Scholarship and Research Excellence in 2017.This international award recognizes a pre-eminent scholar of African studies for their research and scholarly achievement. 

Chuku’s 2017 Ali Mazrui Award. Photo courtesy of Chuku.

Enriching UMBC

In addition to her research, Chuku has been a vibrant part of the UMBC community. As affiliate professor in gender, women’s, and sexuality studies and language, literacy, and culture, she has served on their undergraduate and doctoral program advisory committees, respectively. She has also served on the Provost’s Advisory Committee on Interdisciplinary Activities. 

In 2018 Chuku organized an international conference at UMBC on the history and legacy of women’s roles in the Nigeria-Biafra War. The conference brought renowned scholars and activists from Nigeria, South Africa, Germany, England, Canada, and the United States to UMBC.

UMBC students have also benefited from the intellectual and cultural opportunities Chuku has cultivated at the University. Chuku revived UMBC’s participation in the Model African Union and created the annual Taste of Africa, a celebration of Black History Month and African cultural heritage through unique cuisine and culinary traditions.

Model African Union (2020) in front of the Embassy of Liberia. Photo courtesy of Chuku.

More broadly within the University System of Maryland (USM), Chuku also serves on the executive council of the USM Women’s Forum.

USM Women’s Forum 2019 retreat. Photo courtesy of Natasha Rodriguez.

Liptz Lecture

Similar to previous Lipitz Professorship recipients, Chuku will share her work with the campus community through the Lipitz Lecture. The lecture is the culminating event of the professorship, part of the Humanities Forum lecture series hosted by the Dresher Center for the Humanities. 

Chuku follows Jessica Berman, professor of English and director of the Dresher Center for the Humanities, the 2019 – 2020 Lipitz Professor, and Dan Bailey, a professor of visual arts who focuses on animation and interactive media, the 2018 – 2019 recipient.

“Dr. Chuku is recognized worldwide as a leader in her field,” shares CAHSS Dean Scott Casper. “Her service to UMBC and the national and international research community is wide-ranging and deep. I am delighted that she is this year’s recipient of the Lipitz Professorship.”

Banner image: Chuku at UMBC. Photo courtesy of Marlayna Demond ’11 for UMBC.

Dipanjan Pan, professor of chemical, biochemical, and environmental engineering, has received two new grants from the National Institutes of Health to support research poised to improve COVID-19 testing. 

Pan and his team recently developed an experimental diagnostic test to rapidly detect the novel coronavirus causing COVID-19, potentially as early as the first day of infection. The test shows results visually, through a color change visible with the naked eye when the virus is present. Their preliminary results were published in the journal ACS Nano, and the biosensors behind this work have generated substantial academic and commercial interest.

Pan received funding from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) to support the development of a mediated colorimetric biosensor. This technology greatly reduces the possibility of misinterpreting the results of COVID-19 sensing tests. 

“These awards are very timely. Two back-to-back grants from NIBIB will help me to further develop and optimize the technology and help cover the cost for conducting a clinical study for validation purposes,” says Pan. “The key here is the fine balance between the accuracy of the results and the ability of the testing platform to provide a rapid response.” 

The second grant will support Pan’s work to develop a COVID-19 diagnostic platform that will work like a home-based glucometer. Currently, with limitations in sample collection and transportation, it often takes several days for patients to receive their COVID-19 test results. The delay between when the test is taken and when the results are available can lead to the continued spread of the virus. 

To reduce the time between when a person takes a COVID-19 test and receives their results, Pan will develop a test that includes an electrochemical biosensor that can detect the virus in about 3 minutes. If patients can receive their results within minutes of taking the test, Pan notes, they can quickly self-isolate and avoid exposing others to the virus.

Pan explains that the test will limit the possibility for inaccurate results. “We adopted a molecularly targeted approach to detect RNA from the virus. Since every living organism has unique RNA, targeting a distinctive genetic material of COVID-19 causative virus SARS-CoV-2 ensures remarkable accuracy and specificity,” he says.

In addition to his appointment at UMBC, Pan is a professor of diagnostic radiology and nuclear medicine and pediatrics at the University of Maryland School of Medicine as part of his dual appointment with the University of Maryland, Baltimore.

Banner image: UMBC’s Interdisciplinary Life Sciences Building. Photo by Marlayna Demond ’11 for UMBC.