Quinine

Quinine is a naturally occurring extract of the bark of the Cinchona tree, and has been used for centuries in treating fevers and malaria. However, more recent literature has revealed that quinine is also a broad spectrum antiviral agent. Quinine has been shown to increase the expression of immunity linked genes during Dengue virus infection and to reduce viral replication by up to 80% (1), and has also shown promise in preventing and treating Herpes Simplex virus infection and potentially HIV infection (2) by reducing viral absorption and multiplication (3).

There is also some preliminary indication that the mechanism of quinine's antiviral action may inhibit coronavirus infections. A structural analogue of quinine, chloroquine, has been trialed against 2019 SARS-Cov-2 (the causative agent of COVID19) and found to be very effective (4). Coronaviruses rely on endosomes and lysosomes to replicate, acidifying their lumen to generate an environment conducive towards their replication. They are particularly reliant on lysosomal proteases to cleave their spike proteins, allowing them to fuse with cell membranes and go on to infect further cells (5). Chloroquine is taken up by lysosomes and endosomes and protects against their acidification, and as a result significantly interferes with the ability for coronaviruses to replicate and enter new cells (6). It has been suggested that quinine functions via the same mechanism, actively accumulating in lysosomes (7), reducing lysosomal protease activity and protecting against lysosomal acidification (8).

There is also some evidence that quinine has antibacterial activity (9).

Chloroquine has been demonstrated to in fact accelerate replication of one very specific virus, Semliki forest virus (10). While this result has not been replicated with quinine, in the case of this very specific virus (present in some African countries) chloroquine and its analogues should not be used without further research. However, given the wealth of evidence to support the use of quinine in many other viral diseases, it is still a very promising treatment candidate for these other viral diseases, including coronaviruses.

1 - Malakar, S., Sreelatha, L., Dechtawewat, T., Noisakran, S., Yenchitsomanus, P. T., Chu, J. J. H., & Limjindaporn, T. (2018). Drug repurposing of quinine as antiviral against dengue virus infection. Virus research, 255, 171-178.

2 - Baroni, A., Paoletti, I., Ruocco, E., Ayala, F., Corrado, F., Wolf, R., & Donnarumma, G. (2007). Antiviral effects of quinine sulfate on HSV-1 HaCat cells infected: analysis of the molecular mechanisms involved. Journal of dermatological science, 47(3), 253-255.

3 - Wolf, R., Baroni, A., Greco, R., Corrado, F., Ruocco, E., Tufano, M. A., & Ruocco, V. (2003). Quinine sulfate and HSV replication. Dermatology online journal, 9(3), 3-3.

4 - Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., & Xiao, G. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research, 30(3), 269-271.

5 - Zheng, Y., Shang, J., Yang, Y., Liu, C., Wan, Y., Geng, Q., & Li, F. (2018). Lysosomal proteases are a determinant of coronavirus tropism. Journal of virology, 92(24), e01504-18.

6 - Al‐Bari, M. A. A. (2017). Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacology research & perspectives, 5(1).

7 - Sanchez, C. P., Stein, W. D., & Lanzer, M. (2008). Dissecting the components of quinine accumulation in Plasmodium falciparum. Molecular microbiology, 67(5), 1081-1093.

8 - Lie, S. O., & Schofield, B. (1973). Inactivation of lysosomal function in normal cultured human fibroblasts by chloroquine. Biochemical pharmacology, 22(23), 3109-3114.

9 - Kharal, S. A., Hussain, Q., & Ali, S. (2009). Quinine is bactericidal. J Pak Med Assoc, 59(4).

10 - Seth, P., Mani, H., Singh, A. K., Banaudha, K. K., Madhavan, S., Sidhu, G. S., & Maheshwari, R. K. (1999). Acceleration of viral replication and up-regulation of cytokine levels by antimalarials: implications in malaria-endemic areas. The American journal of tropical medicine and hygiene, 61(2), 180-186.

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Quinine