scholarly journals The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raveen Rathnasinghe ◽  
Sonia Jangra ◽  
Lisa Miorin ◽  
Michael Schotsaert ◽  
Clifford Yahnke ◽  
...  

AbstractThe germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.

2021 ◽  
Author(s):  
Clifford J Yahnke ◽  
Raveen J Rathnasinghe ◽  
Adolfo Garcia-Sastre

Germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit its use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be not effective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) as well as the influenza A virus to 405nm, visible light in the absence of exogenous photosensitizers, indicating a potential porphyrin-independent alternative mechanism of visible light mediated viral inactivation. Given that visible light is generally safe to humans, our results support further exploration of the use of visible light technology for the application of continuous decontamination in areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.


2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Karen N. Barnard ◽  
Brynn K. Alford-Lawrence ◽  
David W. Buchholz ◽  
Brian R. Wasik ◽  
Justin R. LaClair ◽  
...  

ABSTRACT Sialic acids (Sia) are the primary receptors for influenza viruses and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C-4, C-7, C-8, and C-9 positions and N-acetyl or N-glycolyl at C-5. They can also vary in their linkages, including α2-3 or α2-6 linkages. Here, we analyze the distribution of modified Sia in cells and tissues of wild-type mice or in mice lacking CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme, which synthesizes N-glycolyl (Neu5Gc) modifications. We also examined the variation of Sia forms on erythrocytes and in saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal (GI) tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a high degree of variability in display of modified Sia between different species. IAV HAs from different virus strains showed consistently reduced binding to both Neu5Gc- and O-acetyl-modified Sia; however, while IAV NAs were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV and may affect both pathogens and the normal flora of different mucosal sites. IMPORTANCE Sialic acids (Sia) are involved in numerous different cellular functions and are receptors for many pathogens. Sia come in chemically modified forms, but we lack a clear understanding of how they alter interactions with microbes. Here, we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably among different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.


2012 ◽  
Vol 86 (17) ◽  
pp. 9035-9043 ◽  
Author(s):  
J. N. Weeks-Gorospe ◽  
H. R. Hurtig ◽  
A. R. Iverson ◽  
M. J. Schuneman ◽  
R. J. Webby ◽  
...  

2021 ◽  
Author(s):  
Tyler Cuthbert ◽  
Siobhan Ennis ◽  
Stefania F. Musolino ◽  
Heather L. Buckley ◽  
Masahiro Niikura ◽  
...  

<p>The SARS-CoV-2 pandemic has highlighted the weaknesses of relying on single-use mask and respirator personal protective equipment (PPE) and the global supply chain that supports this market. There have been no major innovations in filter technology for PPE in the past two decades. Non-woven textiles used for filtering PPE are single-use products in the healthcare environment; use and protection is focused on preventing infection from airborne or aerosolized pathogens such as Influenza A virus SARS-CoV-2. Recently, C–H bond activation under mild and controllable conditions was reported for crosslinking commodity aliphatic polymers such as polyethylene and polypropylene. Significantly, these are the same types of polymers used in PPE filtration systems. In this report, we take advantage of this C–H insertion method to covalently attach a photosensitizing zinc-porphyrin to the surface of a melt-blow non-woven textile filter material. With the photosensitizer covalently attached to the surface of the textile, illumination with visible light was expected to produce oxidizing <sup>1</sup>O<sub>2</sub>/ROS at the surface of the material that would result in pathogen inactivation. The filter was tested for its ability to inactivate Influenza A virus, an enveloped RNA virus similar to SARS-CoV-2, over a period of four hours with illumination of high intensity visible light. The photosensitizer-functionalized polypropylene filter inactivated our model virus by 99.99% in comparison to a control.</p>


2019 ◽  
Author(s):  
Karen N. Barnard ◽  
Brynn K. Alford-Lawrence ◽  
David W. Buchholz ◽  
Brian R. Wasik ◽  
Justin R. LaClair ◽  
...  

ABSTRACTSialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or N-glycolyl at C5. They can also vary in their linkages, including α2-3 or α2-6-linkages. Here, we analyzed the distribution of modified Sia in cells and tissues of wild-type mice, or in mice lacking cytidine 5’-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) enzyme that synthesizes N-glycolyl modifications (Neu5Gc). We also examined the variation of Sia forms on erythrocytes and saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a great degree of variability in display of modified Sia between different species. IAV HA from different virus strains showed consistently reduced binding to both Neu5Gc and O-acetyl modified Sia; however, while IAV NA were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV, and may affect both pathogens and the normal flora of different mucosal sites.IMPORTANCESialic acids (Sia) are involved in many different cellular functions and are receptors for many pathogens. Sia come in many chemically modified forms but we lack a clear understanding of how they alter the interactions with microbes. Here we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably between different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.


Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 581 ◽  
Author(s):  
Yejin Jang ◽  
Jin Soo Shin ◽  
Joo-Youn Lee ◽  
Heegwon Shin ◽  
Sang Jick Kim ◽  
...  

Influenza A virus, one of the major human respiratory pathogens, is responsible for annual seasonal endemics and unpredictable periodic pandemics. Despite the clinical availability of vaccines and antivirals, the antigenic diversity and drug resistance of this virus makes it a persistent threat to public health, underlying the need for the development of novel antivirals. In a cell culture-based high-throughput screen, a β2-adrenergic receptor agonist, nylidrin, was identified as an antiviral compound against influenza A virus. The molecule was effective against multiple isolates of subtype H1N1, but had limited activity against subtype H3N2, depending on the strain. By examining the antiviral activity of its chemical analogues, we found that ifenprodil and clenbuterol also had reliable inhibitory effects against A/H1N1 strains. Field-based pharmacophore modeling with comparisons of active and inactive compounds revealed the importance of positive and negative electrostatic patterns of phenyl aminoethanol derivatives. Time-of-addition experiments and visualization of the intracellular localization of nucleoprotein NP demonstrated that an early step of the virus life cycle was suppressed by nylidrin. Ultimately, we discovered that nylidrin targets hemagglutinin 2 (HA2)-mediated membrane fusion by blocking conformational change of HA at acidic pH. In a mouse model, preincubation of a mouse-adapted influenza A virus (H1N1) with nylidrin completely blocked intranasal viral infection. The present study suggests that nylidrin could provide a core chemical skeleton for the development of a direct-acting inhibitor of influenza A virus entry.


2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Sarah E. Lauterbach ◽  
Sarah W. Nelson ◽  
Meghann E. Robinson ◽  
Josh N. Lorbach ◽  
Jacqueline M. Nolting ◽  
...  

Abstract Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.


Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 48
Author(s):  
Joanne Haney ◽  
Kieran Dee ◽  
Colin Loney ◽  
Swetha Vijayakrishnan ◽  
Pablo R. Murcia

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are important respiratory pathogens that share common epidemiological features and cellular tropism within the respiratory tract. This gives rise to the potential for biological interactions between IAV and RSV during coinfection of hosts. Virus–virus interactions are increasingly recognised for their contribution to viral dynamics during infection, however, the molecular processes underpinning these interactions are unknown. Here, we developed an in vitro coinfection system to characterise the infection dynamics of IAV (A/Puerto Rico/8/34, H1N1) and RSV (A2) in single virus infection or coinfection in lung epithelial cells, with the aim to identify biological processes that drive virus–virus interactions during coinfection. We compared viral replication kinetics at different multiplicities of infection and observed that RSV replication was inhibited during coinfection with IAV, whilst IAV replication was facilitated by coinfection. To further characterise IAV/RSV interactions, we determined the relative proportions of single virus infected or coinfected cells during early and late timepoints post-infection and observed differences in expression of viral proteins between single and coinfected states. Additionally, cell viability was measured determine differences in viral-induced cytopathic effect. Compared with RSV infection, cell death is induced at earlier timepoints post IAV infection and coinfection, indicating that different cellular processes are initiated in response to infection. These studies highlight that both competitive and facilitative ecological interactions occur between IAV and RSV during coinfection and shed light on sources of potential interactions at the cellular and molecular level.


2021 ◽  
Author(s):  
Tyler Cuthbert ◽  
Siobhan Ennis ◽  
Stefania F. Musolino ◽  
Heather L. Buckley ◽  
Masahiro Niikura ◽  
...  

<p>The SARS-CoV-2 pandemic has highlighted the weaknesses of relying on single-use mask and respirator personal protective equipment (PPE) and the global supply chain that supports this market. There have been no major innovations in filter technology for PPE in the past two decades. Non-woven textiles used for filtering PPE are single-use products in the healthcare environment; use and protection is focused on preventing infection from airborne or aerosolized pathogens such as Influenza A virus SARS-CoV-2. Recently, C–H bond activation under mild and controllable conditions was reported for crosslinking commodity aliphatic polymers such as polyethylene and polypropylene. Significantly, these are the same types of polymers used in PPE filtration systems. In this report, we take advantage of this C–H insertion method to covalently attach a photosensitizing zinc-porphyrin to the surface of a melt-blow non-woven textile filter material. With the photosensitizer covalently attached to the surface of the textile, illumination with visible light was expected to produce oxidizing <sup>1</sup>O<sub>2</sub>/ROS at the surface of the material that would result in pathogen inactivation. The filter was tested for its ability to inactivate Influenza A virus, an enveloped RNA virus similar to SARS-CoV-2, over a period of four hours with illumination of high intensity visible light. The photosensitizer-functionalized polypropylene filter inactivated our model virus by 99.99% in comparison to a control.</p>


2019 ◽  
Vol 476 (6) ◽  
pp. 1005-1008
Author(s):  
Fernando Villalón-Letelier ◽  
Patrick C. Reading

Abstract Moloney leukemia virus 10 (MOV10) is an interferon-inducible RNA helicase that has been implicated in a broad range of cellular functions, including modulating the replication of a diverse range of viruses. However, the mechanisms by which MOV10 promotes or inhibits the replication of particular viruses have not been well defined. A recent paper published in the Biochemical Journal by Li et al. [Biochem. J. (2019) 476, 467–481] provides insight regarding the mechanisms by which MOV10 restricts influenza A virus (IAV) infection in host cells. First, the authors confirm that MOV10 binds to the viral nucleoprotein (NP) and sequesters the viral ribonucleoprotein complex in cytoplasmic granules called processing (P)-bodies, thus inhibiting IAV replication. Second, they demonstrate that the non-structural (NS)1 protein of IAV can act as an antagonist of MOV10, inhibiting the association of MOV10 with NP and promoting MOV10 degradation through the lysosomal pathway. Further research will determine if cellular RNA helicases such as MOV10 represent suitable targets for the development of novel anti-IAV therapies.


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