TMPRSS2, a novel host-directed drug target against SARS-CoV-2

Keller, Christian; Böttcher‐Friebertshäuser, Eva; Lohoff, Michael

doi:10.1038/s41392-022-01084-x

Cited by 9 publications

(5 citation statements)

References 5 publications

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“…Loss of the multibasic S1/S2 CS attenuated SARS-CoV-2 and prevented transmission [50⁎⁎] . In agreement with that, deletions of the S1/S2 CS have been shown to arise naturally only at very low levels, and all variants of concern have retained the R-R-A-R motif at the S1/S2 junction 26 , 50 . The underlying molecular mechanism remains to be determined.…”

Section: Origin Of the Multibasic Cleavage Site In Covssupporting

confidence: 72%

“…Lack of TMPRSS2 expression prevents multicycle replication and pathogenesis of IAVs as well as SARS-CoV, MERS-CoV and SARS-CoV-2 in mice 22 , 23 , 24 , 25 . This demonstrates that TMPRSS2 provides a promising drug target for therapeutic treatment [26] . Interestingly, multicycle replication of a chimeric MERS-CoV bearing the S protein of a MERS-like virus from Ugandan bats required addition of exogenous trypsin to human Caco-2 cells, whereas MERS-CoV replicated trypsin-independent in the cells, most likely due to S cleavage by TMPRSS2.…”

Section: Tmprss2: Virus Activation and Beyondmentioning

confidence: 86%

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The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation

Heindl

Böttcher‐Friebertshäuser

2023

Current Opinion in Virology

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Section: Origin Of the Multibasic Cleavage Site In Covssupporting

confidence: 72%

Section: Tmprss2: Virus Activation and Beyondmentioning

confidence: 86%

The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation

Heindl

Böttcher‐Friebertshäuser

2023

Current Opinion in Virology

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“…Therefore, ACE2 ( 32 ), S proteins ( 33 ), N proteins, TMPRSS2 ( 34 ), RBD, PL pro , M pro /3CL pro ( 35 ), and Nsps are all key to blocking SARS-CoV-2.…”

Section: Severe Acute Respiratory Syndrome Coronavirus Typementioning

confidence: 99%

Recent advances in the exploration and discovery of SARS-CoV-2 inhibitory peptides from edible animal proteins

Kong,

Wang,

Zhong

et al. 2024

Front. Nutr.

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The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), is spreading worldwide. Although the COVID-19 epidemic has passed its peak of transmission, the harm it has caused deserves our attention. Scientists are striving to develop medications that can effectively treat COVID-19 symptoms without causing any adverse reactions. SARS-CoV-2 inhibitory peptides derived from animal proteins have a wide range of functional activities in addition to safety. Identifying animal protein sources is crucial to obtaining SARS-CoV-2 inhibitory peptides from animal sources. This review aims to reveal the mechanisms of action of these peptides on SARS-CoV-2 and the possibility of animal proteins as a material source of SARS-CoV-2 inhibitory peptides. Also, it introduces the utilization of computer-aided design methods, phage display, and drug delivery strategies in the research on SARS-CoV-2 inhibitor peptides from animal proteins. In order to identify new antiviral peptides and boost their efficiency, we recommend investigating the interaction between SARS-CoV-2 inhibitory peptides from animal protein sources and non-structural proteins (Nsps) using a variety of technologies, including computer-aided drug approaches, phage display techniques, and drug delivery techniques. This article provides useful information for the development of novel anti-COVID-19 drugs.

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“…Combination inhibitor therapies targeting TMPRSS2 and furin (aprotinin or MI-432 and MI-1851) have shown enhanced antiviral activity against SARS-CoV-2 in human airway cells compared with controls [ 81 ]. Furthermore, Yang et al recently showed that bruceine A and gamabufotalin, when used together in the nanomolar range, could block the replication of the Delta and Omicron variants of SARS-CoV-2 [ 82 ].…”

Section: Bats Pangolins Parasites and Diarylamidines: Making The Conn...mentioning

confidence: 99%

COVID-19 and Diarylamidines: The Parasitic Connection

Hulme

2023

IJMS

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As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of “post-COVID-19 syndrome” and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with ‘post-COVID-19 syndrome’ require investigation. This review begins with an overview of the parasitic–diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.

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TMPRSS2, a novel host-directed drug target against SARS-CoV-2

Cited by 9 publications

References 5 publications

The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation

The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation

Recent advances in the exploration and discovery of SARS-CoV-2 inhibitory peptides from edible animal proteins

COVID-19 and Diarylamidines: The Parasitic Connection

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