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1.
ACS Appl Mater Interfaces ; 14(4): 4892-4898, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1633913

ABSTRACT

This paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-CoV-2 by visible light irradiation in solution or as a solid coating on paper wipes and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups gives outstanding performance in both the killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-methyl imidazolium groups enhances the light activation process for both E. coli and SARS-CoV-2 but dampens the killing of the bacteria and eliminates the inactivation of the virus in the dark. For the studies with this oligomer in solution at a concentration of 1 µg/mL and E. coli, we obtain 3 log killing of the bacteria with 10 min of irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 µg/mL, we observe 4 log inactivation (99.99%) in 5 min of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated paper wipes and glass fiber filter supports. The SARS-CoV-2 is also inactivated by oligomer-coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/therapy , SARS-CoV-2/radiation effects , COVID-19/genetics , COVID-19/virology , Cations/pharmacology , Escherichia coli/drug effects , Escherichia coli/radiation effects , Humans , Light , Phototherapy , SARS-CoV-2/pathogenicity , Ultraviolet Rays , Virus Inactivation/drug effects , Virus Inactivation/radiation effects
2.
Sci Rep ; 11(1): 20398, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1469993

ABSTRACT

SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS-CoV-2R18 particles engage basal-state integrins. Furthermore, we demonstrate that Mn2+, which induces integrin extension, enhances cell entry of SARS-CoV-2R18. We also show that one class of integrin antagonist, which binds to the αI MIDAS site and stabilizes the inactive, closed conformation, selectively inhibits the engagement of SARS-CoV-2R18 with basal state integrins, but is ineffective against Mn2+-activated integrins. RGD-integrin antagonists inhibited SARS-CoV-2R18 binding regardless of integrin activation status. Integrins transmit signals bidirectionally: 'inside-out' signaling primes the ligand-binding function of integrins via a talin-dependent mechanism, and 'outside-in' signaling occurs downstream of integrin binding to macromolecular ligands. Outside-in signaling is mediated by Gα13. Using cell-permeable peptide inhibitors of talin and Gα13 binding to the cytoplasmic tail of an integrin's ß subunit, we demonstrate that talin-mediated signaling is essential for productive infection.


Subject(s)
COVID-19/metabolism , Integrins/metabolism , SARS-CoV-2/physiology , Virus Internalization , Animals , Chlorocebus aethiops , Host-Pathogen Interactions , Humans , Signal Transduction , Vero Cells
3.
Elife ; 102021 08 03.
Article in English | MEDLINE | ID: covidwho-1339712

ABSTRACT

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform correlates with protection from severe COVID-19. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests that early control of SARS-CoV-2 replication through OAS1 p46 is an important determinant of COVID-19 severity.


Subject(s)
2',5'-Oligoadenylate Synthetase/metabolism , COVID-19/virology , SARS-CoV-2/metabolism , Animals , COVID-19/immunology , CRISPR-Cas Systems , Cell Line , Gene Editing , Humans , Polymorphism, Single Nucleotide , SARS-CoV-2/isolation & purification
4.
Exp Biol Med (Maywood) ; 246(8): 952-959, 2021 04.
Article in English | MEDLINE | ID: covidwho-992323

ABSTRACT

The ongoing pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed a substantial strain on the supply of personal protective equipment, particularly the availability of N95 respirators for frontline healthcare personnel. These shortages have led to the creation of protocols to disinfect and reuse potentially contaminated personal protective equipment. A simple and inexpensive decontamination procedure that does not rely on the use of consumable supplies is dry heat incubation. Although reprocessing with this method has been shown to maintain the integrity of N95 respirators after multiple decontamination procedures, information on the ability of dry heat incubation to inactivate SARS-CoV-2 is largely unreported. Here, we show that dry heat incubation does not consistently inactivate SARS-CoV-2-contaminated N95 respirators, and that variation in experimental conditions can dramatically affect viability of the virus. Furthermore, we show that SARS-CoV-2 can survive on N95 respirators that remain at room temperature for at least five days. Collectively, our findings demonstrate that dry heat incubation procedures and ambient temperature for five days are not viable methods for inactivating SARS-CoV-2 on N95 respirators for potential reuse. We recommend that decontamination procedures being considered for the reuse of N95 respirators be validated at each individual site and that validation of the process must be thoroughly conducted using a defined protocol.


Subject(s)
COVID-19 , Hot Temperature , Masks , Pandemics , SARS-CoV-2/metabolism , Virus Inactivation , Animals , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/prevention & control , COVID-19/therapy , Chlorocebus aethiops , Humans , Vero Cells
5.
ACS Appl Mater Interfaces ; 12(50): 55688-55695, 2020 Dec 16.
Article in English | MEDLINE | ID: covidwho-955892

ABSTRACT

In the present study, we examined the inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by synthetic conjugated polymers and oligomers developed in our laboratories as antimicrobials for bacteria, fungi, and nonenveloped viruses. The results show highly effective light-induced inactivation with several of these oligomers and polymers including irradiation with near-UV and visible light. In the best case, one oligomer induced a 5-log reduction in pfu/mL within 10 min. In general, the oligomers are more active than the polymers; however, the polymers are active with longer wavelength visible irradiation. Although not studied quantitatively, the results show that in the presence of the agents at concentrations similar to those used in the light studies, there is essentially no dark inactivation of the virus. Because three of the five materials/compounds examined are quaternary ammonium derivatives, this study indicates that conventional quaternary ammonium antimicrobials may not be active against SARS-CoV-2. Our results suggest several applications involving the incorporation of these materials in wipes, sprays, masks, and clothing and other personal protection equipment that can be useful in preventing infections and the spreading of this deadly virus and future outbreaks from similar viruses.


Subject(s)
Polymers/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19/virology , Chlorocebus aethiops , Humans , Light , Polymers/radiation effects , SARS-CoV-2/pathogenicity , SARS-CoV-2/radiation effects , Ultraviolet Rays , Vero Cells , Virus Inactivation/drug effects , Virus Inactivation/radiation effects
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