Wonder of wonders, miracle of miracles: the unprecedented speed of COVID-19 science

Saag, Michael S.

doi:10.1152/physrev.00010.2022

Cited by 14 publications

(7 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the introduction of several effective vaccines, the mutagenicity and transmissibility of SARS-CoV-2, as evidenced by the emergence of several variants, make the understanding of the pathophysiological mechanism involved and the identification of therapeutic agents an extremely high priority ( 9 ). COVID-19 is mainly a respiratory disease but it can lead to other systemic effects and eventually to a systemic disorder ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan

Mobley

Molyvdas

Kojima

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants, COVID-19 has led to 651,918,402 confirmed cases, and 6,656,601 deaths worldwide (as of December 27, 2022; https://covid19.who.int/). Despite advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in the proteome of alveolar type II (ATII)-like Rat L2 cells that lack ACE2 receptors. Systems biology analysis revealed that the S1 induced proteomics changes were associated with three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. We also found that pre-treatment of L2 cells with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects on the proteome. Western blotting analysis and cell cycle measurements confirmed the S1-upregulation of E2F1 and ROCK2/RhoA in L2 cells and the protective effects of HMW-HA. Taken as a whole, our studies revealed profound and novel biological changes that contribute to our current understanding of both S1 and Hyaluronan biology. This data shows that the S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury (236 words).

show abstract

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan

Mobley

Molyvdas

Kojima

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…5 Although the development of COVID-19 vaccines played a central role in controlling the current pandemic, the development of efficacious antiviral drugs is critically important for reducing morbidity and hospitalization thus saving lives. 6,7 At the outset, many different strategies and approaches were being pursued including de novo drug development, drug repurposing, and monoclonal antibody therapy development. 8,9 Efforts directed toward drug repurposing led to the development and approval of Remdesivir and Molnupiravir, which target viral enzyme RNAdependent RNA polymerase (RdRp).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of optically active SARS-CoV-2 Mpro inhibitor drug nirmatrelvir (Paxlovid): an approved treatment of COVID-19

Ghosh

Yadav

2023

Org. Biomol. Chem.

View full text Add to dashboard Cite

show abstract

“…Recently there have been reports that the SARS-CoV-2 spike protein interacts with other receptors as well, like CD147(63). Despite the introduction of several effective vaccines, the mutagenicity and transmissibility of SARS-CoV-2, as evidenced by the emergence of several variants, makes the understanding of the pathophysiological mechanism involved and the identification of therapeutic agents an extremely high priority (55). COVID-19 is mainly a respiratory disease but it can lead to other systemic effects and eventually to a systemic disorder (29).…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

Mobley

Molyvdas

Kojima

et al. 2022

Preprint

View full text Add to dashboard Cite

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.

show abstract

Wonder of wonders, miracle of miracles: the unprecedented speed of COVID-19 science

Cited by 14 publications

References 72 publications

The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan

The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan

Synthesis of optically active SARS-CoV-2 Mpro inhibitor drug nirmatrelvir (Paxlovid): an approved treatment of COVID-19

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

Contact Info

Product

Resources

About