Researchers Discover How the COVID-19 Virus Hijacks and Rapidly Damages Human Lung Cells

Researchers Discover How the COVID-19 Virus Hijacks and Rapidly Damages Human Lung Cells

Researchers determine clinically authorized medicines that may be re-purposed for COVID-19 therapy.

In a multi-group collaborative involving the Nationwide Rising Infectious Illness Laboratories (NEIDL), the Middle for Regenerative Medication (CReM), and the Middle for Community Techniques Biology (CNSB), scientists have reported the first map of the molecular responses of human lung cells to an infection by SARS-CoV-2. By combining bioengineered human alveolar cells with refined, extremely exact mass spectrometry expertise, Boston College College of Medication (BUSM) researchers have recognized host proteins and pathways in lung cells whose ranges change upon an infection by the SARS-CoV-2, offering insights into illness pathology and new therapeutic targets to dam COVID-19.

They discovered an important kind of protein modification known as “phosphorylation” turns into aberrant in these contaminated lung cells. Phosphorylation of proteins play a serious position in regulating protein operate inside the cells of an organism and each protein abundance and protein phosphorylation are sometimes extremely managed processes in the case of regular/wholesome cells. Nonetheless, they found that SARS-CoV-2 throws the lung cells into disarray, inflicting irregular modifications in protein quantities and frequency of protein phosphorylation inside these cells. These irregular modifications assist the virus to multiply finally destroy the cells. The destruction of contaminated cells might lead to widespread lung harm.

In accordance with the researchers, as quickly as the SARS-CoV-2 enters the lung cells, it quickly begins to take advantage of the cell’s core assets, that are in any other case required for the cell’s regular development and operate. “The virus makes use of these assets to proliferate whereas evading assault by the physique’s immune system. On this method new viruses type which subsequently exit the exhausted and brutally broken lung cell, leaving them to self-destruct. These new viruses then infect different cells, the place the similar cycle is repeated,” explains corresponding writer Andrew Emili, PhD, professor of biochemistry at BUSM.

The researchers examined lung alveolar cells from one to 24 hours after an infection with SARS-CoV-2 to grasp what modifications happen in lung cells instantly (at one, three and six hours after an infection by SARS-CoV-2) and what modifications happen later (at 24 hours after an infection). These modifications have been then in comparison with uninfected cells. All proteins from contaminated and uninfected alveolar cells, similar to the totally different time-points have been extracted and labeled with distinctive barcoding tags known as “tandem mass tag.” These tags, which may be precisely detected solely by a mass spectrometer, allow strong quantification of protein and phosphorylation abundance in cells.

“Our outcomes confirmed that compared to regular/uninfected lung cells, SARS-CoV-2 contaminated lung cells confirmed dramatic modifications in the abundance of 1000’s of proteins and phosphorylation occasions,” mentioned Darrell Kotton, MD, professor of pathology & laboratory drugs at BUSM and director of the CReM.

“Furthermore, our knowledge additionally confirmed that the SARS-CoV-2 virus induces a major variety of these modifications as early as one hour submit an infection and lays the basis for an entire hijack of the host lung cells,” provides Elke Mühlberger, PhD, affiliate professor of microbiology and principal investigator at the NEIDL.

“There are essential organic options particular to lung cells that aren’t reproduced by different cell varieties generally used to check viral an infection,” mentioned Andrew Wilson, MD, affiliate professor of drugs at BUSM and CReM investigator. “Finding out the virus in the context of the cell kind that’s most broken in sufferers is prone to yield insights that we wouldn’t have the ability to see in different mannequin programs.”

The researchers additionally analyzed their knowledge to determine potential alternatives for COVID-19 therapy and discovered that not less than 18 pre-existing clinically authorized medicine (developed initially for different medical circumstances/illnesses) may be probably re-purposed to be used in direction of COVID-19 remedy. These medicine have proven distinctive promise to dam the proliferation of the SARS-CoV-2 in lung cells.


The researchers consider this info is invaluable and paves the method for newer, probably promising and extra importantly, an economical and time-saving therapeutic technique to fight COVID-19.

Researchers Raghuveera Kumar Goel, PhD; Adam Hume, PhD; Jessie Huang, PhD; Kristy Abo, BA; Rhiannon Werder, PhD and Ellen Suder, BS, additionally contributed to those findings.

These findings seem on-line in the journal Molecular Cell.

Reference: “Actionable Cytopathogenic Host Responses of Human Alveolar Sort 2 Cells to SARS-CoV-2” by Ryan M. Hekman, Adam J. Hume, Raghuveera Kumar Goel, Kristine M. Abo, Jessie Huang, Benjamin C. Blum, Rhiannon Bree Werder, Ellen L. Suder, Indranil Paul, Sadhna Phanse, Ahmed Youssef, Kostantinos D. Alysandratos, Dzmitry Padhorny, Sandeep Ojha, Alexandra Mora-Martin, Dmitry Kretov, Peter Ash, Mamta Varma, Jian Zhao, J.J. Patten, Carlos Villacorta-Martin, Dante Bolzan, Carlos Perea-Resa, Esther Bullitt, Anne Hinds, Andrew Tilston-Lunel, Xaralabos Varelas, Shaghayegh Farhangmehr, Ulrich Braunschweig, Julian H. Kwan, Mark McComb, Avik Basu, Mohsan Saeed, Valentina Perissi, Eric J. Burks, Matthew D. Layne, John H. Connor, Robert Davey, Ji-Xin Cheng, Benjamin L. Wolozin, Benjamin J. Blencowe, Stefan Wuchty, Shawn M. Lyons, Dima Kozakov, Daniel Cifuentes, Michael Blower, Darrell N. Kotton, Andrew A. Wilson, Elke Mühlberger and Andrew Emili, 19 November 2020, Molecular Cell.
DOI: 10.1016/j.molcel.2020.11.028

Funding was supplied by NIH F30HL147426 to Okay.M.A.; CJ Martin Fellowship from the Australian NHMRC to R.B.W.; IM Rosenzweig Award, Pulmonary Fibrosis Basis to Okay.D.A.; NIH AG056318, AG064932, AG061706, and AG050471 to B.L.W.; NIH RM1 GM135136 and R21GM127952 and NSF AF1816314 to D. Kozakov; Evergrande MassCPR, Digital Transformation Institute Award, and NIH R01HL128172, R01HL095993, R01HL122442, U01HL134745, and U01HL134766 to D.N.Okay.; CIHR, COVID-19 Motion Initiative to B.J.B.; NIH HL007035T32 to E.L.S.; NIH R01AI125453, P01AI120943, and R01AI128364 and Massachusetts Consortium on Pathogen Readiness to J.J.P. and R.D.; NIH U01TR001810, UL1TR001430, R01DK101501, and R01DK117940 to A.A.W.; Quick Grants, Evergrande MassCPR, and NIH R01AI133486, R21AI135912, R21AI137793, and R21AI147285 to E.M.; and NIH 1UL1TR001430, RO1AG064932, and RO1AG061706 to A.E.

Disclosures: B.L.W. declares a place as CSO of Aquinnah Prescription drugs. A.E. and D.N.Okay. declare business funding from Johnson & Johnson, Merck, and Novartis.

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