Hydroxychloroquine and the Coronavirus: Connecting the Dots Through the Biology Knowledge Graph


Hydroxychloroquine and the Coronavirus: Connecting the Dots Through the Biology Knowledge Graph

It would be hard to miss the current interest in finding effective treatment for COVID-19. In this regard, the combination of hydroxychloroquine (HCQ) with azithromycin is getting a great deal of attention. HCQ, sold under the brand name Plaquenil, is a well-known anti-malarial drug, while azithromycin is a common antibiotic that is usually used for the treatment of strep throat (the widely used Zithromax, Z-Pak).

Quinine (CQ), extracted from the bark of the cinchona trees found in the tropical Andean forests of western South America, was widely used in the 19th century to treat malaria infections that commonly arise in the tropics. The synthetically produced derivative drugs of quinine, chloroquine and the more recently produced hydroxychloroquine, are widely used to prevent and treat malaria but also used off-label for the treatment of rheumatoid arthritis and lupus.

A small clinical trial conducted in the south of France produced encouraging results on the use of the hydroxychloroquine and azithromycin combination for the treatment of COVID-19 [4]. This was further supported by preliminary experiments showing the ability of CQ and HCQ to inhibit SARS-CoV-2 activity in vitro [1, 2]. In addition to these published data, there is a large amount of anecdotal data from frontline physicians treating COVID-19 in New York and California, who are enthusiastic about the responses they have gotten using combinations of HCQ, azithromycin and zinc.



Hydroxychloroquine and the Coronavirus: Connecting the Dots Through the Biology Knowledge Graph

Then, we compared the overall effects of these drugs on ARDS-induced proteins with those of non-steroidal anti-inflammatory (NSAID) drugs from our previous analysis (analgesics and ARDS). The complete results are shown in Table 1. Ascorbic acid (vitamin C), a nutraceutical, and aspirin, a common analgesic, were the strongest inhibitors based on their overall relationship with ARDS-induced proteins (Table 1A).<!--td {border: 1px solid #ccc;}br {mso-data-placement:same-cell;}-->hydroxychloroquine for lupushydroxychloroquine arthritis

In contrast, similar to our previous analysis, acetaminophen was the strongest activator of ARDS-induced proteins. On the other hand, chloroquine and aspirin were the two strongest inhibitors when looking at the total number of references supporting a particular drug’s profile of activity on all the ARDS-induced proteins. This could be related to the fact that these two drugs have been studied more extensively compared to the other drugs. Interestingly, azithromycin moved up the list of inhibitors in Table 1B, suggesting a large literature around the interaction between this drug and ARDS proteins.

ARDS is a characteristic of the late stages of an unresolved coronavirus infection, namely Stage III or Hyperinflammation Phase (Figure 2).hydroxychloroquine price



Hydroxychloroquine and the Coronavirus: Connecting the Dots Through the Biology Knowledge Graph

Hence, it occurred to us to identify the direct effects of HCQ and azithromycin on the core proteins of hyperinflammation. These proteins include major inflammatory response mediators such as the neutrophil chemoattractant CXCL8; immunoregulatory cytokines such as IL1B, IL2, IL4, IL6 and IL10; the proinflammatory protein TNF; the mediator of cellular response to viral infections IFNG; and the cytotoxicity signaling molecule IL12. Together these proteins can initiate and control both acute and chronic inflammation.


Hydroxychloroquine and the Coronavirus: Connecting the Dots Through the Biology Knowledge Graph

credited to ELSEVIER

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