Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial

Okugawa, Shu; Ikeda, Mahoko; Kashiwabara, Kosuke; Moritoyo, Takashi; Kohsaka, Takao; Shimizu, Toshio; Hagiya, Hideharu; Hasegawa, Kou; Otsuka, Fumio; Miwa, Ayumi; Kisimoto, Nobuhito; Mizoguchi, Ayako; Imamura, Akira; Ikeuchi, Kazuhiko; Tsutsumi, Takeya; Jubishi, Daisuke; Hashimoto, Hideki; Okamoto, Koh; Harada, Sohei; Inoue, Jun-ichiro; Seto, Yasuyuki; Moriya, Kyoji

doi:10.1016/j.ijantimicag.2023.106922

Cited by 5 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A meta-analysis revealed a significant correlation between TMPRSS2 rs12329760 C-allele and an elevated risk of developing severe COVID-19 ( Saengsiwaritt et al., 2022 ). This result may be explained by positive correlation between TMPRSS2 activity and viral load ( Okugawa et al., 2023 ). A genome-wide association study (GWAS) identified that a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), is associated with severe COVID-19 in patients less than 65 years of age ( Namkoong et al., 2022 ).…”

Section: Host Genetic Factors In Sars-cov-2 Susceptibility and Covid-...mentioning

confidence: 99%

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Zhang,

Chen,

Tian

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.

show abstract

Section: Host Genetic Factors In Sars-cov-2 Susceptibility and Covid-...mentioning

confidence: 99%

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

Zhang,

Chen,

Tian

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…However, clinical trials with nafamostat mesylate and camostat mesylate failed in improving the clinical outcomes of COVID-19 hospitalization patients, possibly due to their short plasma half-life (1 h for camostat mesylate and 23.1 min for nafamostat mesylate) and the multiple entry pathways of SARS-CoV-2 during infection ( Midgley et al, 1994 ; Tsukagoshi, 2000 ; Gunst et al, 2021 ; Zhuravel et al, 2021 ; Kinoshita et al, 2022 ). However, it was reported that nafamostat mesylate significantly decreases the viral load in the nasopharyngeal sample of mild early-onset COVID-19 patients ( Okugawa et al, 2023 ). Considering the structural and functional similarity, the working mechanism of camostat mesylate is expected to be similar to the nafamostat.…”

Section: Proteolytic Cleavage Stepmentioning

confidence: 99%

Structural understanding of SARS-CoV-2 virus entry to host cells

Le,

Kannappan,

Kim

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.

show abstract