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1.
Chem Commun (Camb) ; 58(11): 1804-1807, 2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1639537

ABSTRACT

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Peptide Fragments/pharmacology , Peptidomimetics/pharmacology , SARS-CoV-2/drug effects , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Cell Line, Tumor , Humans , Microbial Sensitivity Tests , Peptide Fragments/chemical synthesis , Peptide Fragments/metabolism , Peptidomimetics/chemical synthesis , Peptidomimetics/metabolism , Protein Binding , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
2.
J Med Chem ; 64(23): 17486-17495, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1531976

ABSTRACT

The pandemic of acute respiratory disease in 2019 caused by highly pathogenic and infectious SARS-CoV-2 has seriously endangered human public safety. The 6-HB (HR1-HR2 complex) formation occurring in the process of spike protein-mediated membrane fusion could serve as a conserved and potential target for the design of fusion inhibitors. Based on the HR2 domain of 6-HB, we designed and synthesized 32 stapled peptides using an all-hydrocarbon peptide stapling strategy. Owing to the improved proteolytic stability and higher helical contents, the optimized stapled peptides termed SCH2-1-20 and SCH2-1-27 showed better inhibitory activities against pseudo and authentic SARS-CoV-2 compared to the linear counterpart. Of note, SCH2-1-20 and SCH2-1-27 were proved to interfere with S protein-mediated membrane fusion. Structural modeling indicated similar binding modes between SCH2-1-20 and the linear peptide. These optimized stapled peptides could serve as potent fusion inhibitors in treating and preventing SARS-CoV-2, and the corresponding SAR could facilitate further optimization.


Subject(s)
Spike Glycoprotein, Coronavirus , Membrane Fusion , Pandemics , Protein Binding
3.
Environ Sci Technol ; 55(9): 6239-6247, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1169372

ABSTRACT

White wastes (unseparated plastics, face masks, textiles, etc.) pose a serious challenge to sustainable human development and the ecosystem and have recently been exacerbated due to the surge in plastic usage and medical wastes from COVID-19. Current recycling methods such as chemical recycling, mechanical recycling, and incineration require either pre-sorting and washing or releasing CO2. In this work, a carbon foam microwave plasma process is developed, utilizing plasma discharge to generate surface temperatures exceeding ∼3000 K in a N2 atmosphere, to convert unsorted white wastes into gases (H2, CO, C2H4, C3H6, CH4, etc.) and small amounts of inorganic minerals and solid carbon, which can be buried as artificial "coal". This process is self-perpetuating, as the new solid carbon asperities grafted onto the foam's surface actually increase the plasma discharge efficiency over time. This process has been characterized by in situ optical probes and infrared sensors and optimized to handle most of the forms of white waste without the need for pre-sorting or washing. Thermal measurement and modeling show that in a flowing reactor, the device can achieve locally extremely high temperatures, but the container wall will still be cold and can be made with cheap materials, and thus, a miniaturized waste incinerator is possible that also takes advantage of intermittent renewable electricity.


Subject(s)
COVID-19 , Refuse Disposal , Carbon , Ecosystem , Humans , Hydrocarbons , Microwaves , SARS-CoV-2
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