Potent antiviral effect of silver nanoparticles on SARS-CoV-2

doi:10.1016/j.bbrc.2020.09.018

. 2020 Nov 26;533(1):195-200.

doi: 10.1016/j.bbrc.2020.09.018. Epub 2020 Sep 11.

Potent antiviral effect of silver nanoparticles on SARS-CoV-2

Sundararaj S Jeremiah¹, Kei Miyakawa¹, Takeshi Morita¹, Yutaro Yamaoka², Akihide Ryo³

Affiliations

¹ Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan.
² Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan; Life Science Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Kanagawa, 259-1146, Japan.
³ Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan. Electronic address: aryo@yokohama-cu.ac.jp.

PMID: 32958250
PMCID: PMC7486059
DOI: 10.1016/j.bbrc.2020.09.018

Potent antiviral effect of silver nanoparticles on SARS-CoV-2

Sundararaj S Jeremiah et al. Biochem Biophys Res Commun. 2020.

. 2020 Nov 26;533(1):195-200.

doi: 10.1016/j.bbrc.2020.09.018. Epub 2020 Sep 11.

Authors

Sundararaj S Jeremiah¹, Kei Miyakawa¹, Takeshi Morita¹, Yutaro Yamaoka², Akihide Ryo³

Affiliations

¹ Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan.
² Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan; Life Science Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Kanagawa, 259-1146, Japan.
³ Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan. Electronic address: aryo@yokohama-cu.ac.jp.

PMID: 32958250
PMCID: PMC7486059
DOI: 10.1016/j.bbrc.2020.09.018

Abstract

The pandemic of COVID-19 is spreading unchecked due to the lack of effective antiviral measures. Silver nanoparticles (AgNP) have been studied to possess antiviral properties and are presumed to inhibit SARS-CoV-2. Due to the need for an effective agent against SARS-CoV-2, we evaluated the antiviral effect of AgNPs. We evaluated a plethora of AgNPs of different sizes and concentration and observed that particles of diameter around 10 nm were effective in inhibiting extracellular SARS-CoV-2 at concentrations ranging between 1 and 10 ppm while cytotoxic effect was observed at concentrations of 20 ppm and above. Luciferase-based pseudovirus entry assay revealed that AgNPs potently inhibited viral entry step via disrupting viral integrity. These results indicate that AgNPs are highly potent microbicides against SARS-CoV-2 but should be used with caution due to their cytotoxic effects and their potential to derange environmental ecosystems when improperly disposed.

Keywords: COVID-19; Colloidal silver; SARS-CoV-2; Silver nanoparticles.

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Conflict of interest statement

Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article. Y.Y. is a current employee of Kanto Chemical Co., Inc.

Figures

**Fig. 1**
**Cytotoxicity of colloidal Silver on mammalian cells 1A**: Cytotoxicity exhibited by serial concentrations of colloidal silver on VeroE6/TMPRSS2 cells. 1B: Cytotoxicity exhibited by serial concentrations of colloidal silver on Calu-3 cells.

**Fig. 2**
Concentration and dose dependent antiviral effect of naked Silver nanoparticles on SARS-CoV-2.2A: Colloidal Silver rescues VeroE6/TMPRSS2 cells from SARS-CoV-2 mediated cell death in a concentration dependent manner. Error bars obtained from triplicate testing. p value ≤ 0.005 (∗∗∗). **2B:** Concentration dependent inhibition of SARS-CoV-2 replication in Calu-3 cells by colloidal Silver. Error bars obtained from triplicate testing. p value ≤ 0.001 (∗∗∗). 2C: Silver nanoparticles exhibit size-dependent antiviral action against SARS-CoV-2 in Vero/TMPRSS2 cells. Error bars obtained from triplicate testing. p value ≤ 0.005 (∗∗∗). 2D: Size-dependent viral inhibition of SARS-CoV-2 by Silver nanoparticles in Calu-3 cells. Error bars obtained from triplicate testing. p value ≤ 0.001 (∗∗∗).

**Fig. 3**
Silver nanoparticles effectively inhibit extracellular SARS-CoV-2.3A: Schematic representation of virus pre-treatment assay (top panel), cell post-treatment assay (central panel) and cell pre-treatment assay (bottom panel). 3B: Performance of PVP coated 10 nm Silver nanoparticles in the three study designs with respect to rescue of cells from SARS-CoV-2 infection. Error bars obtained from triplicate testing. p value ≤ 0.005 (∗∗∗). 2C: Performance of PVP coated 10 nm Silver nanoparticles in the three study designs with respect to reduction of SARS-CoV-2 replication. Error bars obtained from triplicate testing. p value ≤ 0.001 (∗∗∗).

**Fig. 4**
Characteristics of PVP coated 10 nm Silver nanoparticles in SARS-CoV-2 infection. 4A: Immunofluorescence imaging comparing the effect of 10 nm and 100 nm Silver nanoparticles against SARS-CoV-2 infection in VeroE6/TMPRSS2 cells. Cell nuclei (blue) and SARS-CoV-2 nucleocapsid protein in cytoplasm (red). NC - Negative control. 4B: PVP coated 10 nm Silver nanoparticles protect VeroE6/TMPRSS2 cells from SARS-CoV-2 infection mediated cell death. Crystal violet staining reveals partial protection with visible plaques (red arrowheads) and complete protection with absence of plaques (black arrowheads). 4C: Pseudovirus entry assay. PVP coated 10 nm Silver nanoparticles inhibit entry of pseudovirus in VeroE6/TMPRSS2 cells. NC - Negative control, nAb - Neutralizing antibody. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

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References

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[1] Galdiero S., Falanga A., Vitiello M., Cantisani M., Marra V., Galdiero M. Silver nanoparticles as potential antiviral agents. Mol. Basel Switz. 2011;16:8894–8918. - PMC - PubMed

[2] Galdiero S., Falanga A., Vitiello M., Cantisani M., Marra V., Galdiero M. Silver nanoparticles as potential antiviral agents. Mol. Basel Switz. 2011;16:8894–8918. - PMC - PubMed

[3] Han J., Chen L., Duan S.-M., Yang Q.-X., Yang M., Gao C., Zhang B.-Y., He H., Dong X.-P. Efficient and quick inactivation of SARS coronavirus and other microbes exposed to the surfaces of some metal catalysts. Biomed. Environ. Sci. BES. 2005;18:176–180. - PubMed

[4] Han J., Chen L., Duan S.-M., Yang Q.-X., Yang M., Gao C., Zhang B.-Y., He H., Dong X.-P. Efficient and quick inactivation of SARS coronavirus and other microbes exposed to the surfaces of some metal catalysts. Biomed. Environ. Sci. BES. 2005;18:176–180. - PubMed

[5] Talebian S., Wallace G.G., Schroeder A., Stellacci F., Conde J. Nanotechnology-based disinfectants and sensors for SARS-CoV-2. Nat. Nanotechnol. 2020;15:618–621. - PubMed

[6] Talebian S., Wallace G.G., Schroeder A., Stellacci F., Conde J. Nanotechnology-based disinfectants and sensors for SARS-CoV-2. Nat. Nanotechnol. 2020;15:618–621. - PubMed

[7] Matsuyama S., Nao N., Shirato K., Kawase M., Saito S., Takayama I., Nagata N., Sekizuka T., Katoh H., Kato F., Sakata M., Tahara M., Kutsuna S., Ohmagari N., Kuroda M., Suzuki T., Kageyama T., Takeda M. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc. Natl. Acad. Sci. U.S.A. 2020;117:7001–7003. - PMC - PubMed

[8] Matsuyama S., Nao N., Shirato K., Kawase M., Saito S., Takayama I., Nagata N., Sekizuka T., Katoh H., Kato F., Sakata M., Tahara M., Kutsuna S., Ohmagari N., Kuroda M., Suzuki T., Kageyama T., Takeda M. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc. Natl. Acad. Sci. U.S.A. 2020;117:7001–7003. - PMC - PubMed

[9] Gordon D.E., Jang G.M., Bouhaddou M., Xu J., Obernier K., White K.M., O’Meara M.J., Rezelj V.V., Guo J.Z., Swaney D.L., Tummino T.A., Hüttenhain R., Kaake R.M., Richards A.L., Tutuncuoglu B., Foussard H., Batra J., Haas K., Modak M., Kim M., Haas P., Polacco B.J., Braberg H., Fabius J.M., Eckhardt M., Soucheray M., Bennett M.J., Cakir M., McGregor M.J., Li Q., Meyer B., Roesch F., Vallet T., Mac Kain A., Miorin L., Moreno E., Naing Z.Z.C., Zhou Y., Peng S., Shi Y., Zhang Z., Shen W., Kirby I.T., Melnyk J.E., Chorba J.S., Lou K., Dai S.A., Barrio-Hernandez I., Memon D., Hernandez-Armenta C., Lyu J., Mathy C.J.P., Perica T., Pilla K.B., Ganesan S.J., Saltzberg D.J., Rakesh R., Liu X., Rosenthal S.B., Calviello L., Venkataramanan S., Liboy-Lugo J., Lin Y., Huang X.-P., Liu Y., Wankowicz S.A., Bohn M., Safari M., Ugur F.S., Koh C., Savar N.S., Tran Q.D., Shengjuler D., Fletcher S.J., O’Neal M.C., Cai Y., Chang J.C.J., Broadhurst D.J., Klippsten S., Sharp P.P., Wenzell N.A., Kuzuoglu-Ozturk D., Wang H.-Y., Trenker R., Young J.M., Cavero D.A., Hiatt J., Roth T.L., Rathore U., Subramanian A., Noack J., Hubert M., Stroud R.M., Frankel A.D., Rosenberg O.S., Verba K.A., Agard D.A., Ott M., Emerman M., Jura N., von Zastrow M., Verdin E., Ashworth A., Schwartz O., d’Enfert C., Mukherjee S., Jacobson M., Malik H.S., Fujimori D.G., Ideker T., Craik C.S., Floor S.N., Fraser J.S., Gross J.D., Sali A., Roth B.L., Ruggero D., Taunton J., Kortemme T., Beltrao P., Vignuzzi M., García-Sastre A., Shokat K.M., Shoichet B.K., Krogan N.J. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459–468. - PMC - PubMed

[10] Gordon D.E., Jang G.M., Bouhaddou M., Xu J., Obernier K., White K.M., O’Meara M.J., Rezelj V.V., Guo J.Z., Swaney D.L., Tummino T.A., Hüttenhain R., Kaake R.M., Richards A.L., Tutuncuoglu B., Foussard H., Batra J., Haas K., Modak M., Kim M., Haas P., Polacco B.J., Braberg H., Fabius J.M., Eckhardt M., Soucheray M., Bennett M.J., Cakir M., McGregor M.J., Li Q., Meyer B., Roesch F., Vallet T., Mac Kain A., Miorin L., Moreno E., Naing Z.Z.C., Zhou Y., Peng S., Shi Y., Zhang Z., Shen W., Kirby I.T., Melnyk J.E., Chorba J.S., Lou K., Dai S.A., Barrio-Hernandez I., Memon D., Hernandez-Armenta C., Lyu J., Mathy C.J.P., Perica T., Pilla K.B., Ganesan S.J., Saltzberg D.J., Rakesh R., Liu X., Rosenthal S.B., Calviello L., Venkataramanan S., Liboy-Lugo J., Lin Y., Huang X.-P., Liu Y., Wankowicz S.A., Bohn M., Safari M., Ugur F.S., Koh C., Savar N.S., Tran Q.D., Shengjuler D., Fletcher S.J., O’Neal M.C., Cai Y., Chang J.C.J., Broadhurst D.J., Klippsten S., Sharp P.P., Wenzell N.A., Kuzuoglu-Ozturk D., Wang H.-Y., Trenker R., Young J.M., Cavero D.A., Hiatt J., Roth T.L., Rathore U., Subramanian A., Noack J., Hubert M., Stroud R.M., Frankel A.D., Rosenberg O.S., Verba K.A., Agard D.A., Ott M., Emerman M., Jura N., von Zastrow M., Verdin E., Ashworth A., Schwartz O., d’Enfert C., Mukherjee S., Jacobson M., Malik H.S., Fujimori D.G., Ideker T., Craik C.S., Floor S.N., Fraser J.S., Gross J.D., Sali A., Roth B.L., Ruggero D., Taunton J., Kortemme T., Beltrao P., Vignuzzi M., García-Sastre A., Shokat K.M., Shoichet B.K., Krogan N.J. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459–468. - PMC - PubMed

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Potent antiviral effect of silver nanoparticles on SARS-CoV-2

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Potent antiviral effect of silver nanoparticles on SARS-CoV-2

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