Journal of Infectious Diseases & Therapy
Open Access

One of the recent letters on potential coronavirus therapeutics from Chinese Academy of Sciences at Wuhan to Nature drew my attention. https://www.nature.com/articles/s41422-020-0282-0/

Among the several chemical drugs that they tested against coronaviral infection in cell culture, an old malaria drug called Chloroquine (CQ) and Remdesivir that inhibits RNA-dependent RNA polymerase (RdRP) appear to be the most potent with IC₅₀ around 1 micro M. Unfortunately, however, mainly due to its side effects and drug-resistance, CQ is no longer used for malaria therapy at least in US, Europe and Japan. However, a few other new anti-malaria chemicals such as Arteminisin (AM), which was developed by Youyou Tu in China, a 2015 Nobel laureate and Hydroxylchloroquine (HQ), are in the market for malaria therapy.

Very interestingly, it is well known that both malaria and viral infection in general need the major “pathogenic” kinase (PAK1) in hosts, and all these anti-malaria drugs indeed block PAK1 [1]. I have been working on both PAK1 and anti-PAK1 chemicals for more than 25 years, since the first RAC/CDC42-activated kinase (PAK1) was cloned from mammals in 1994 [2]. https:// www.somatopublications.com/pathogenic-roles-of-pak1-includingoncogenesis- and-ageing.pdf

The following are two major scientific evidences for PAK1- dependency of coronaviral infection: (i) Very recently a team at Colorado University found that a tumor suppressor phosphatase called PTEN, which inactivates PAK1, suppresses the coronavirus-induced CCL2-dependent fibrosis of lungs [3], and (ii) a decade ago a team in Taipei found that CCL2 expression depends on coronaviral receptor called ACE2 (angiotensin converting enzyme 2) –CK2/RAS-PAK1- RAF-AP1 signalling pathway [4] (Figure 1).

Figure 1: PTEN, a PAK1-blocker, interferes with coronavirus – induced PAK1-dependent signalling pathway leading to lung fibrosis.

In addition to the above anti-malaria drugs, there are several natural or synthetic PAK1-blockers which are readily available in the market: a bee product called propolis, Melatonin from pineal glands, Ivermectin, Triptolide from thunder god vine (a Chinese traditional medicine), an old pain-killer called Ketorolac and so on [5]. In addition, these PAK1- blockers stimulate antiviral immune systems (Ab production) in hosts which are normally suppressed by PAK1 [6] Thus, they would be potentially better than its vaccine alone. I hope the WHO, NIH and other medical officials take this outsider’s wisdom for a tip to tackle or ease the current pandemic corona-virus outbreaks, before its specific vaccine becomes available in the end.

Alternatively, since a group at Alberta University in Canada also confirmed that an ATP analog called Remdesivir or GS-5734 (Figure 2) which selectively inhibits RNA-dependent RNA polymerase (RdRP) derived from this RNA virus is also effective to suppress its replication [7], NIH has recently started the clinical trials of Remdesivir for COVID-19 patients. GS-5734 was originally developed for the potential treatment of Ebola virus in 2019 by Gilead Sciences in California [7].

Figure 2: Chemical structure of Remdesivir (GS-5734).