Our Strategy

Antivirals and SARS-CoV-2

At PrimerGen, we are focused on the development of research–based cures for presently unmet medical needs. Chief among this is the need for an effective, safe and cheap antiviral treatment for COVID–19.
Numerous medications are currently being evaluated for the treatment of COVID–19. These include: Remdesevir (an ATP-analog originally developed for the treatment of Ebola by Gilead Sciences), Chloroquine and its derivative Hydroxychloroquine (alkalinizing agents used against malaria, amebiasis, rheumatoid arthritis and lupus erythematosus) and Lopinavir (a protease inhibitor developed by AbbVie for the treatment of HIV-1 infections used in combination with Ritonavir). These three drugs have shown promising antiviral activity against SARS–CoV–2 in vitro (Jeon et al., 2020) with IC50 values in the low micromolar range (Remdesevir IC50 = 11.41 µM; Chloroquine IC50 = 7.28 µM; Lopinavir IC50 = 9.12 µM).
Another less talked-about medication called Niclosamide (marketed under various names, including Niclocide, Niclosan, Phenasal and Fenasal) also seems to hold some promise in the treatment of COVID–19.
The potential of Niclosamide in the treatment of COVID-19 is discussed below.

Niclosamide and SARS-CoV-2

Niclosamide (IUPAC name: 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydrobenzamidine), originally developed by the German Multinational Pharmaceutical and Life Sciences company Bayer AG in the 1960s, is an antiparasitic medication used for the treatment of tapeworm infections, such as diphyllobothriasis, hymenolepsiasis and taeniasis (Anand, 1997).
Niclosamide is both cheap and safe (with minimal side-effects) and features in the list of essential medicines by the WHO. Importantly, Niclosamide exhibits potent antiviral activity in vitro against coronaviruses. Niclosamide efficiently blocks the replication of SARS–CoV–2 in vitro at submicromolar concentrations (IC50 = 280 nM), with negligible cytotoxicity (Jeon et al., 2020). Niclosamide also efficiently blocks the replication of SARS-1 coronavirus, at similar concentrations (IC50 ~ 300 nM) (Wu et al., 2004).
At PrimerGen, we have extensive experience working with Niclosamide. Our research group has previously unravelled the mechanism-of-action of this drug, as described in (Fonseca et al., 2012). We firmly believe that Niclosamide (or derivatives of this drug) may hold some promise as an antiviral medication against SARS-CoV-2.
At PrimerGen, we are working hard to understand Niclosamide as a novel treatment against COVID-19.

Medical Disclosure

Do not under any circumstance take the information published herein as medical advice. We do not recommend you (or anyone) taking any of the medication listed in this website without prior consultation with your Physician (Medical Doctor). Taking the above-mentioned medications without medical supervision may cause serious harm or even death. Under no circumstances is PrimerGen Therapeutics (or its members) to be held responsible for any consequence resulting from administration of the above-described medications.

Bibliography

Anand N. (1997) Approaches to Design and Synthesis of Antiparasitic Drugs. PharmacoChemistry Library 25. Elsevier. Pages 239-251

Fonseca, B.D., Diering, G.H., Bidinosti, M.A., Dalal, K., Alain, T., Balgi, A.D., Forestieri, R., Nodwell, M., Rajadurai, C.V., Gunaratnam, C., Tee, A.R., Duong, F., Andersen, R.J., Orlowski, J., Numata, M., Sonenberg, N., Roberge, M., 2012. Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling. J. Biol. Chem. 287, 17530–17545. https://doi.org/10.1074/jbc.M112.359638

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., Huettenhain, 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, 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., 2020. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. https://doi.org/10.1038/s41586-020-2286-9

Jeon, S., Ko, M., Lee, J., Choi, I., Byun, S.Y., Park, S., Shum, D., Kim, S., 2020. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Antimicrob. Agents Chemother. https://doi.org/10.1128/AAC.00819-20

Wu, C.-J., Jan, J.-T., Chen, C.-M., Hsieh, H.-P., Hwang, D.-R., Liu, H.-W., Liu, C.-Y., Huang, H.-W., Chen, S.-C., Hong, C.-F., Lin, R.-K., Chao, Y.-S., Hsu, J.T.A., 2004. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob. Agents Chemother. 48, 2693–2696. https://doi.org/10.1128/AAC.48.7.2693-2696.2004