The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue "Recent Advances in Herpesviruses Research: What's in the Pipeline?" aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.

Department of Applied Ecology Faculty of Environmental Sciences Czech University of Life Sciences Prague Kamýcká 129 6 Suchdol 16521 Prague Czech Republic

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World Health Organization Coronavirus disease (COVID-2019) situation reports 2020. [(accessed on 15 April 2020)]; Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.

Liu C., Zhou Q., Li Y., Garner L.V., Watkins S.P., Carter L.J., Smoot J., Gregg A.C., Daniels A.D., Jervey S., et al. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. ACS Cent. Sci. 2020;6:315–331. doi: 10.1021/acscentsci.0c00272. PubMed DOI PMC

Baglivo M., Baronio M., Natalini G., Beccari T., Chiurazzi P., Fulcheri E., Petralia P.P., Michelini S., Fiorentini G., Miggiano G.A., et al. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: A possible strategy for reducing SARS-COV-2 infectivity? Acta Biomed. 2020;91:161–164. PubMed PMC

Čulenová M., Sychrová A., Hassan S.T.S., Berchová-Bímová K., Svobodová P., Helclová A., Michnová H., Hošek J., Vasilev H., Suchý P., et al. Multiple In vitro biological effects of phenolic compounds from Morus alba root bark. J. Ethnopharmacol. 2020;248:112296. doi: 10.1016/j.jep.2019.112296. PubMed DOI

Hassan S.T.S., Šudomová M., Berchová-Bímová K., Šmejkal K., Echeverría J. Psoromic Acid, a Lichen-Derived Molecule, Inhibits the Replication of HSV-1 and HSV-2, and Inactivates HSV-1 DNA Polymerase: Shedding Light on Antiherpetic Properties. Molecules. 2019;24:2912. doi: 10.3390/molecules24162912. PubMed DOI PMC

Wu K., Chen L., Peng G., Zhou W., Pennell C.A., Mansky L.M., Geraghty R.J., Li F. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses. J. Virol. 2011;85:5331–5337. doi: 10.1128/JVI.02274-10. PubMed DOI PMC

Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;S0092-8674:30229–30234. doi: 10.1016/j.cell.2020.02.052. PubMed DOI PMC

Brezáni V., Leláková V., Hassan S.T.S., Berchová-Bímová K., Nový P., Klouček P., Maršík P., Dall’Acqua S., Hošek J., Šmejkal K. Anti-Infectivity against Herpes Simplex Virus and Selected Microbes and Anti-Inflammatory Activities of Compounds Isolated from Eucalyptus globulus Labill. Viruses. 2018;10:360. doi: 10.3390/v10070360. PubMed DOI PMC

Hassan S.T.S., Berchová-Bímová K., Petráš J., Hassan K.T.S. Cucurbitacin B interacts synergistically with antibiotics against Staphylococcus aureus clinical isolates and exhibits antiviral activity against HSV-1. S. Afr. J. Bot. 2017;108:90–94. doi: 10.1016/j.sajb.2016.10.001. DOI

Choy K.T., Wong A.Y., Kaewpreedee P., Sia S.F., Chen D., Hui K.P.Y., Chu D.K.W., Chan M.C.W., Cheung P.P., Huang X., et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:104786. doi: 10.1016/j.antiviral.2020.104786. PubMed DOI PMC

Kantarjian H.M., O’Brien S., Cortes J. Homoharringtonine/omacetaxine mepesuccinate: The long and winding road to food and drug administration approval. Clin. Lymphoma Myeloma Leuk. 2013;13:530–533. doi: 10.1016/j.clml.2013.03.017. PubMed DOI PMC

Lü S., Wang J. Homoharringtonine and omacetaxine for myeloid hematological malignancies. J. Hematol. Oncol. 2014;7:2. doi: 10.1186/1756-8722-7-2. PubMed DOI PMC

Dong H.J., Wang Z.H., Meng W., Li C.C., Hu Y.X., Zhou L., Wang X.J. The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo. Viruses. 2018;10:601. doi: 10.3390/v10110601. PubMed DOI PMC

Kim J.E., Song Y.J. Anti-varicella-zoster virus activity of cephalotaxine esters in vitro. J. Microbiol. 2019;57:74–79. doi: 10.1007/s12275-019-8514-z. PubMed DOI PMC

Möller M., Herzer K., Wenger T., Herr I., Wink M. The alkaloid emetine as a promising agent for the induction and enhancement of drug-induced apoptosis in leukemia cells. Oncol. Rep. 2007;18:737–744. doi: 10.3892/or.18.3.737. PubMed DOI

Grollman A.P. Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics. Proc. Natl. Acad. Sci. USA. 1966;56:1867–1874. doi: 10.1073/pnas.56.6.1867. PubMed DOI PMC

Andersen P.I., Krpina K., Ianevski A., Shtaida N., Jo E., Yang J., Koit S., Tenson T., Hukkanen V., Anthonsen M.W., et al. Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine. Viruses. 2019;11:964. doi: 10.3390/v11100964. PubMed DOI PMC

Mukhopadhyay R., Roy S., Venkatadri R., Su Y.P., Ye W., Barnaeva E., Mathews G.L., Southall N., Hu X., Wang A.Q., et al. Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus. PLoS Pathog. 2016;12:e1005717. doi: 10.1371/journal.ppat.1005717. PubMed DOI PMC

Khandelwal N., Chander Y., Rawat K.D., Riyesh T., Nishanth C., Sharma S., Jindal N., Tripathi B.N., Barua S., Kumar N. Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants. Antiviral Res. 2017;144:196–204. doi: 10.1016/j.antiviral.2017.06.006. PubMed DOI

Treml J., Gazdová M., Šmejkal K., Šudomová M., Kubatka P., Hassan S.T.S. Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development. Viruses. 2020;12:154. doi: 10.3390/v12020154. PubMed DOI PMC

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