University of California San Diego Health

Experimental Therapy for Parasitic Heart Disease May Also Help Stop COVID-19

By blocking human enzyme cathepsin L, chemical inhibitor K777 reduces coronavirus’ ability to infect cell lines; clinical trials are underway

Newswise — James McKerrow, MD, PhD, dean of the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego, has long studied neglected tropical diseases — chronic and disabling parasitic infections that primarily affect poor and underserved communities in developing nations. They’re called “neglected” because there is little financial incentive for pharmaceutical companies to develop therapies for them.

One of these neglected diseases is Chagas disease, the leading cause of heart failure in Latin America, which is spread by “kissing bugs” carrying the parasite Trypanosoma cruzi. These parasites produce an enzyme called cruzain that helps them replicate and evade the human immune system. McKerrow’s research team looks for inhibitors of cruzain — small molecules that might form the basis for new anti-parasitic medicines. One particularly effective cruzain inhibitor is called K777.

Then, in the spring of 2020, the COVID-19 pandemic began to sweep through the United States. Researchers quickly reported that SARS-CoV-2, the coronavirus that causes COVID-19, can’t dock on and infect human cells unless a human enzyme called cathepsin L cleaves the virus’ spike protein.

And it just so happens that cathepsin L looks and acts a lot like cruzain.

In a study published March 31, 2021 by ACS Chemical Biology, McKerrow and team show that low concentrations of K777 inhibit cathepsin L can reduce SARS-CoV-2’s ability to infect four host cell lines, without harming the cells.

“Since K777 inhibits a human enzyme, not the virus itself, it’s our hope that it’s less likely the virus will evolve resistance against it,” said McKerrow, co-senior author of the study with Thomas Meek, PhD, of Texas A&M University.

K777 wasn’t equally effective in all cell lines. That’s likely because not all cell lines produced the same amount of cathepsin L or the same amount of ACE2, the host cell receptor that the virus’ spike protein uses to latch onto cells after it’s cleaved by cathepsin L. The inhibitor was best at preventing SARS-CoV-2 infection in the cells that produced the most cathepsin L and ACE2.

The cell lines tested were derived from African green monkey kidney epithelium, human cervical epithelium and two types of human lung epithelium. While an important research tool, cell lines such as these are not necessarily representative of patients. They are easy to grow and manipulate in research laboratories because they are cancer cells, but that also means their molecular features likely differ from the average person’s healthy lung or cervical cells.

“We were surprised at just how effective K777 is in blocking viral infection in the lab,” McKerrow said. “Yet under usual circumstances it would be impractical and unlikely that we ourselves would be able to move the compound so quickly into clinical trials. We’re fortunate that an ‘entrepreneur-in-residence’ program here at UC San Diego has helped bridge that gap.”

Selva Therapeutics, a privately held biotechnology company, has licensed K777 from UC San Diego. In parallel with this study, the company has also found that the experimental therapeutic prevented lung damage in COVID-19 animal models and was well-tolerated by people who participated in a Phase I clinical trial to assess safety. Selva is planning a Phase IIa clinical trial in non-hospitalized COVID-19 patients for late 2021.

Many people with COVID-19 experience mild disease and can recover at home with supportive care to help relieve their symptoms. Currently, severe cases of COVID-19 may be treated with the antiviral drug remdesivir, approved by the U.S. Food and Drug Administration (FDA) for use in hospitalized patients, or a medication that has received emergency use authorization from the FDA, such as monoclonal antibodies. Worldwide, more than 124 million people have been diagnosed with COVID-19 and 2.72 million have died from the infection.

Co-authors of the study include: Drake M. Mellott, Bala C. Chenna, Demetrios H. Kostomiris, Jiyun Zhu, Zane W. Taylor, Klaudia I. Kocurek, Ardala Katzfuss, Linfeng Li, Frank M. Raushel, Texas A&M University; Chien-Te Tseng, Aleksandra Drelich, Jason Hsu, Vivian Tat, University of Texas; Pavla Fajtová, UC San Diego and Academy of Sciences of the Czech Republic; Miriam A. Giardini, Danielle Skinner, Ken Hirata, Michael C. Yoon, Sungjun Beck, Aaron F. Carlin, Alex E. Clark, Laura Beretta, Vivian Hook, Anthony J. O’Donoghue, Jair Lage de Siqueira-Neto, UC San Diego; Daniel Maneval, Felix Frueh, Selva Therapeutics; Brett L. Hurst, and Hong Wang, Utah State University.

Funding for this research came, in part, from the National Institutes of Health (grants N01-AI-30048, R24 AI120942 NPARS-S01), AgriLife Research, Texas A&M University, Burroughs Wellcome Fund and Selva Therapeutics, Inc.

Disclosure: James McKerrow is an advisor to and holds stock shares in Selva Therapeutics, Inc.

###



Filters close

Showing results

110 of 5857
Released: 22-Jun-2021 5:10 PM EDT
Tecnología de inteligencia artificial y ECG puede rápidamente descartar infección por COVID-19
Mayo Clinic

La inteligencia artificial puede ofrecer un manera de determinar con exactitud que una persona no está infectada con la COVID-19. Un estudio internacional y retrospectivo descubrió que la infección por SARS-CoV-2, el virus que causa la COVID-19, provoca sutiles cambios eléctricos en el corazón. Un electrocardiograma (ECG) mediado por inteligencia artificial detecta estos cambios y puede servir como una prueba rápida y confiable para descartar la infección por COVID-19.

Released: 22-Jun-2021 4:45 PM EDT
Penn Medicine to Use $1M from City of Philadelphia for Additional Community Vaccination Clinics
Perelman School of Medicine at the University of Pennsylvania

Penn Medicine will continue its collaboration with the West and Southwest Philadelphia communities to operate a series of COVID-19 vaccine clinics in partnership with community organizations, faith-based institutions, restaurants, barbershops, and even professional sports teams thanks to $1 million in funding from the City of Philadelphia, in partnership with PMHCC.

Released: 22-Jun-2021 12:30 PM EDT
Political Variables Carried More Weight Than Healthcare in Government Response to COVID-19
Binghamton University, State University of New York

Political institutions such as the timing of elections and presidentialism had a larger influence on COVID-19 strategies than the institutions organizing national healthcare, according to a research team led by a professor at Binghamton University, State University of New York.

22-Jun-2021 12:00 PM EDT
Study Testing How Well COVID-19 Vaccine Prevents Infection and Spread of SARS-CoV-2 Among University Students Now Expands to Include Young Adults Beyond the University Setting
Covid-19 Prevention Network (CoVPN)

The Prevent COVID U study, which launched in late March 2021 to evaluate SARS-CoV-2 infection and transmission among university students vaccinated with the Moderna COVID-19 Vaccine, has expanded beyond the university setting to enroll young adults ages 18 through 29 years and will now also include people in this age group who choose not to receive a vaccine.

Newswise: First Wave COVID-19 Data Underestimated Pandemic Infections
18-Jun-2021 8:30 AM EDT
First Wave COVID-19 Data Underestimated Pandemic Infections
American Institute of Physics (AIP)

Two COVID-19 pandemic curves emerged within many cities during the one-year period from March 2020 to March 2021. Oddly, the number of total daily infections reported during the first wave is much lower than that of the second, but the total number of daily deaths reported during the first wave is much higher than the second wave.

Newswise: PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Released: 22-Jun-2021 9:55 AM EDT
PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Pacific Northwest National Laboratory

PNNL researchers used natural language processing and deep learning techniques to reveal how and why different types of misinformation and disinformation spread across social platforms. Applied to COVID-19, the team found that misinformation intended to influence politics and incite fear spreads fastest.

Released: 22-Jun-2021 8:30 AM EDT
Engineering Nanobodies As Lifesavers When SARS-CoV-2 Variants Attack
Ohio State University

Scientists are pursuing a new strategy in the protracted fight against the SARS-CoV-2 virus by engineering nanobodies that can neutralize virus variants in two different ways.

Released: 21-Jun-2021 3:45 PM EDT
Rare Neurological Disorder Documented Following COVID-19 Vaccination
American Neurological Association (ANA)

In two separate articles in the Annals of Neurology, clinicians in India and England report cases of a rare neurological disorder called Guillain-Barré syndrome after individuals were vaccinated against COVID-19.

Newswise: New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
17-Jun-2021 12:10 PM EDT
New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
Harvard Medical School

Risk of SARS-CoV-2 infection increased 30 percent for households with a recent birthday in counties with high rates of COVID-19 Findings suggest informal social gatherings such as birthday parties played role in infection spread at the height of the coronavirus pandemic No birthday-bash infection jumps seen in areas with low rates of COVID-19 Households with children’s birthdays had greater risk of SARS-CoV-2 infection than with adult birthdays

Newswise: COVID-19 dual-antibody therapies effective against variants in animal study
Released: 21-Jun-2021 10:05 AM EDT
COVID-19 dual-antibody therapies effective against variants in animal study
Washington University in St. Louis

A study from Washington University School of Medicine in St. Louis suggests that many, but not all, COVID-19 therapies made from combinations of two antibodies are effective against a wide range of virus variants, and that combination therapies appear to prevent the emergence of drug resistance.


Showing results

110 of 5857

close
2.46774