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Arginine, Malaria, Helminths and Covid,

March 15, 2021 - 20:06 -- Pierre Lutgen

In my recent weblog « Africa, Covid and Schistosomiasis » I documented that eosinophilia is common in helminthic infections (www.malariaworld.org 14/01/2021) and that this might significatly contribute to a protection against viral infections. And that this could explain the low incidence of Covid in tropical African countries.

There is another input which deserves consideration. It appears that arginine depletion induced by malaria and helminthic infections also protects against viral infection.
In schistosomiasis heavily infected mice, serum arginine levels were shown to approach zero A.W. Senft,. Arginine depletion in mammals and snails infected with S. mansoni or S. hematobium,. Comparative Biochemistry and Physiology, Volume 21, Issue 2, 1967, 299-306,
In malaria infections arginine generates NO which kills Plasmodium falciparum parasites. This might be the main reason why the parasites sequester the arginine pool in serum and erythocytes in their vacuole where they metabolize it in the inocuous citrulline. Cobbold SA, Llinás M, Kirk K. Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasite Plasmodium falciparum. Cell Microbiol. 2016 Jun;18(6):820-30. doi: 10.1111/cmi.12552 .

Virus replication is dependent on the availability of amino acids. Arginine is involved in the synthesis of viral proteins
Hübner MP, Layland LE, Hoerauf A. Helminths and their implication in sepsis - a new branch of their immunomodulatory behaviour?. Pathog Dis. 2013;69(2):127-141. doi:10.1111/2049-632X.12080
Inglis VB. Requirement of arginine for the replication of herpes virus. J Gen Virol. 1968 Jul;3(1):9-17. doi: 10.1099/0022-1317-3-1-9. PMID: 4300568.
Garnett HM. The effect of arginine deprivation on the cytopathogenic effect and replication of human cytomegalovirus. Arch Virol. 1975;48(2):131-45. doi: 10.1007/BF01318146. PMID: 167690.

A few months ago the potential of arginine depletion in the fight against COVID-19 has been recognized. It was confirmed that arginine is a key nutrient essential in the life of many viruses. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) relies on conserved arginine residues . Arginine depletion also reduces inflammation in patients
Joseph M. Grimes, Shaheer Khan, Mark Badeaux, Ravi M. Rao. Arginine depletion as a therapeutic approach for patients with COVID-19, International Journal of Infectious Diseases, 2021, 102, Pages 566-570

In 1968 already, the role of arginine in the replication of certain intranuclear DNA viruses had been well documented. Scientific papers demonstrated that arginine is required for the replication of type 2 adenovirus and essential for the multiplication of herpes virus. A study on the simian SV 40 virus showed that the effect of arginine depletion was overwhelmin, but that the depletion of 12 other essential amino acids like lysine, methionine, cyteine, only had negligable effects.

Goldblum N, Ravid Z, Becker Y. Effect of withdrawal of arginine and other amino acids on the synthesis of tumour and viral antigens of SV 40 virus. J Gen Virol. 1968 Jul;3(1):143-6.

It is a shame that this effect discovered 50 years ago was forgotten or neglected by the experts in virology. During the 2020 Covid crisis it deserved as much attention as the development of costly vaccines.