Coronavirus makes changes that cause cells not to recognize it
Discovery lays groundwork for designing novel antiviral drugs

Date:
July 24, 2020
Source:
University of Texas Health Science Center at San Antonio
Summary:
The novel coronavirus changes the appearance of its messenger RNA
cap to trick the host cell into not recognizing it is foreign,
according to a new study.



FULL STORY ==========================================================================
With an alarm code, we can enter a building without bells going off. It
turns out that the SARS coronavirus 2 (SARS-CoV-2) has the same advantage entering cells. It possesses the code to waltz right in.


==========================================================================
On July 24 in Nature Communications, researchers at The University
of Texas Health Science Center at San Antonio (UT Health San Antonio)
reported how the coronavirus achieves this.

The scientists resolved the structure of an enzyme called nsp16, which
the virus produces and then uses to modify its messenger RNA cap, said
Yogesh Gupta, PhD, the study lead author from the Joe R. and Teresa
Lozano Long School of Medicine at UT Health San Antonio.

"It's a camouflage," Dr. Gupta said. "Because of the modifications,
which fool the cell, the resulting viral messenger RNA is now considered
as part of the cell's own code and not foreign." Deciphering the 3D
structure of nsp16 paves the way for rational design of antiviral drugs
for COVID-19 and other emerging coronavirus infections, Dr.

Gupta said. The drugs, new small molecules, would inhibit nsp16 from
making the modifications. The immune system would then pounce on the
invading virus, recognizing it as foreign.

"Yogesh's work discovered the 3D structure of a key enzyme of the COVID-19 virus required for its replication and found a pocket in it that can
be targeted to inhibit that enzyme. This is a fundamental advance in
our understanding of the virus," said study coauthor Robert Hromas, MD, professor and dean of the Long School of Medicine.

Dr. Gupta is an assistant professor in the Department of Biochemistry
and Structural Biology at UT Health San Antonio and is a member of the university's Greehey Children's Cancer Research Institute.

In lay terms, messenger RNA can be described as a deliverer of genetic
code to worksites that produce proteins.

The laboratory of the lead author, Yogesh Gupta, PhD, is supported
through funds from the Max and Minnie Tomerlin Voelcker Foundation,
the San Antonio Area Foundation, The University of Texas System, UT
Health San Antonio, the Greehey Children's Cancer Research Institute of
UT Health San Antonio, and the Cancer Prevention and Research Institute
of Texas (CPRIT).


========================================================================== Story Source: Materials provided by University_of_Texas_Health_Science_Center_at_San_Antonio.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Thiruselvam Viswanathan, Shailee Arya, Siu-Hong Chan, Shan Qi,
Nan Dai,
Anurag Misra, Jun-Gyu Park, Fatai Oladunni, Dmytro Kovalskyy,
Robert A.

Hromas, Luis Martinez-Sobrido, Yogesh K. Gupta. Structural basis
of RNA cap modification by SARS-CoV-2. Nature Communications,
2020; 11 (1) DOI: 10.1038/s41467-020-17496-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200724104157.htm

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