FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3119372242> ?p ?o ?g. }

• W3119372242 abstract "Abstract The coronaviral pandemic is exerting a tremendously detrimental impact on global health, quality of life and the world economy, emphasizing the need for effective medications for current and future coronaviral outbreaks as a complementary approach to vaccines. The Spike protein, responsible for cell receptor binding and viral internalization, possesses multiple disulfide bonds raising the possibility that disulfide-reducing agents might disrupt Spike function, prevent viral entry and serve as effective drugs against SARS-CoV-2. Here we show the first experimental evidence that reagents capable of reducing disulfide bonds can inhibit viral infection in cell-based assays. Molecular dynamics simulations of the Spike receptor-binding domain (RBD) predict increased domain flexibility when the four disulfide bonds of the domain are reduced. This flexibility is particularly prominent for the surface loop, comprised of residues 456-490, which interacts with the Spike cell receptor ACE2. Consistent with this finding, the addition of exogenous disulfide bond reducing agents affects the RBD secondary structure, lowers its melting temperature from 52 to 36-39°C and decreases its binding affinity to ACE2 by two orders of magnitude at 37°C. Finally, the reducing agents dithiothreitol (DTT) and tris (2-carboxyethyl)phosphine (TCEP) inhibit viral replication at high µM – low mM levels with a negligible effect on cell viability at these concentrations. The antiviral effect of monothiol-based reductants N-Acetyl-L-cysteine (NAC) and reduced glutathione (GSH) was not observed due to decreases in cell viability. Our research demonstrates the clear potential for medications that disrupt Spike disulfides as broad-spectrum anticoronaviral agents and as a first-line defense against current and future outbreaks." @default.
• W3119372242 created "2021-01-18" @default.
• W3119372242 creator A5005759921 @default.
• W3119372242 creator A5028738166 @default.
• W3119372242 creator A5041967571 @default.
• W3119372242 creator A5058639044 @default.
• W3119372242 creator A5060467096 @default.
• W3119372242 creator A5075658120 @default.
• W3119372242 creator A5091648479 @default.
• W3119372242 date "2021-01-04" @default.
• W3119372242 modified "2023-10-16" @default.
• W3119372242 title "Spike protein disulfide disruption as a potential treatment for SARS-CoV-2" @default.
• W3119372242 cites W1164264743 @default.
• W3119372242 cites W1511013913 @default.
• W3119372242 cites W1512686244 @default.
• W3119372242 cites W1539248632 @default.
• W3119372242 cites W1589733225 @default.
• W3119372242 cites W1937553338 @default.
• W3119372242 cites W1965435260 @default.
• W3119372242 cites W1966238900 @default.
• W3119372242 cites W1968966170 @default.
• W3119372242 cites W1970357363 @default.
• W3119372242 cites W1976499671 @default.
• W3119372242 cites W1986740222 @default.
• W3119372242 cites W1988424962 @default.
• W3119372242 cites W1992560805 @default.
• W3119372242 cites W1994476763 @default.
• W3119372242 cites W1995670529 @default.
• W3119372242 cites W1997379463 @default.
• W3119372242 cites W1997480152 @default.
• W3119372242 cites W2013090907 @default.
• W3119372242 cites W2015114722 @default.
• W3119372242 cites W2015190256 @default.
• W3119372242 cites W2020565933 @default.
• W3119372242 cites W2027014621 @default.
• W3119372242 cites W2027518730 @default.
• W3119372242 cites W2035687084 @default.
• W3119372242 cites W2039320633 @default.
• W3119372242 cites W2041638382 @default.
• W3119372242 cites W2052955020 @default.
• W3119372242 cites W2054734154 @default.
• W3119372242 cites W2057477511 @default.
• W3119372242 cites W2058203018 @default.
• W3119372242 cites W2058249709 @default.
• W3119372242 cites W2063698972 @default.
• W3119372242 cites W2065662162 @default.
• W3119372242 cites W2067174909 @default.
• W3119372242 cites W2081693079 @default.
• W3119372242 cites W2083412871 @default.
• W3119372242 cites W2094016251 @default.
• W3119372242 cites W2106089413 @default.
• W3119372242 cites W2119111857 @default.
• W3119372242 cites W2120967846 @default.
• W3119372242 cites W2128135911 @default.
• W3119372242 cites W2129801997 @default.
• W3119372242 cites W2131275850 @default.
• W3119372242 cites W2146476111 @default.
• W3119372242 cites W2154385453 @default.
• W3119372242 cites W2160544821 @default.
• W3119372242 cites W2161605421 @default.
• W3119372242 cites W2433555039 @default.
• W3119372242 cites W2586637063 @default.
• W3119372242 cites W2755284350 @default.
• W3119372242 cites W2895574624 @default.
• W3119372242 cites W2917215708 @default.
• W3119372242 cites W2948616961 @default.
• W3119372242 cites W2981663786 @default.
• W3119372242 cites W3005605085 @default.
• W3119372242 cites W3009912996 @default.
• W3119372242 cites W3013800395 @default.
• W3119372242 cites W3014067025 @default.
• W3119372242 cites W3027231799 @default.
• W3119372242 cites W3030752164 @default.
• W3119372242 cites W3037965408 @default.
• W3119372242 cites W3042692818 @default.
• W3119372242 cites W3042922222 @default.
• W3119372242 cites W3044394179 @default.
• W3119372242 cites W3047731046 @default.
• W3119372242 cites W3051261383 @default.
• W3119372242 cites W3073049614 @default.
• W3119372242 cites W3080829430 @default.
• W3119372242 cites W3081435976 @default.
• W3119372242 cites W3084641538 @default.
• W3119372242 cites W3087924281 @default.
• W3119372242 cites W3088139162 @default.
• W3119372242 cites W3092181020 @default.
• W3119372242 cites W3094575957 @default.
• W3119372242 cites W3095170895 @default.
• W3119372242 cites W3112834570 @default.
• W3119372242 doi "https://doi.org/10.1101/2021.01.02.425099" @default.
• W3119372242 hasPublicationYear "2021" @default.
• W3119372242 type Work @default.
• W3119372242 sameAs 3119372242 @default.
• W3119372242 citedByCount "4" @default.
• W3119372242 countsByYear W31193722422021 @default.
• W3119372242 countsByYear W31193722422023 @default.
• W3119372242 crossrefType "posted-content" @default.
• W3119372242 hasAuthorship W3119372242A5005759921 @default.
• W3119372242 hasAuthorship W3119372242A5028738166 @default.
• W3119372242 hasAuthorship W3119372242A5041967571 @default.

• next