Two researchers/physicians out of the University of Naples Federico II—one of the oldest universities in the world—introduce the use of two drugs classically used by dermatologists for the investigational use in fighting SARS-CoV-2, the virus behind the COVID-19 pandemic. The two doctors hypothesize that the use of Hydroxychloroquine (HCQ) and Ivermectin may evidence a consequential and synergistic action if administered simultaneously both for chemoprophylaxis and treatment of COVID-19.
TrialSite News includes the source manuscript and offers below a simple and straightforward breakdown of their position.
Why is HCQ being tested in many clinical trials now against COVID-19?
The Italian doctors posit that HCQ, the antimalarial drug, is an analog of chloroquine (CQ), considered an immunomodulator rather than immunosuppressant. They note that HCQ and CQ inhibit SARS-CoV-2 in vitro, with HCQ found to be more potent than chloroquine (CQ). They go on that HCQ evidences antiviral effects at both pre-infection and post-infection stages. Moreover, they position that HCQ could interfere with glycosylation of angiotensin-converting enzyme 2, thereby reducing the binding efficiency between angiotensin-converting enzyme 2 on host cells and the SARS-CoV-2 spike protein.
They also speculate that HCQ could block virus fusion with the host cell via the inhibition of protease activity in cleaving coronavirus spike proteins. They include their reference sources for review and follow up. Making the claim that HCQ contributes to the “suppression of the ‘cytokine storm’ responsible for the disease progression to acute respiratory distress syndrome by a number of mechanisms, examples include the reduction of T-cell activation and differentiation not to mention decreased production of cytokines by T cells and B cells—they offered no reference for this last point. They concluded their preliminary prose in regards to HCQ that the drug is the center of a number of formal clinical trials to assess the effectiveness of the drug in interfering with SARS-CoV-2.
What about Ivermectin—why consider?
Well they start that the antiparasitic drug frequently prescribed at the dermatology clinic as the primary treatment for lice actually displayed antiviral activity. Its servers to act as a specific inhibitor of importin- α/β– mediated nuclear import. They claim that because of this impact on importin- α/β– mediated nuclear transport of viral proteins, this drug suppresses the replication of several RNA viruses, including HIV, chikungunya virus, and yellow fever virus. This latter point was identified in a published manuscript published in Antiviral Res. 2018; 159: 55-6.
And recently they refer to the Monash University, Australia research demonstrating antiviral action of ivermectin against the SARS-CoV-2 clinical isolate in vitro, with a single dose of the drug able to control viral replication within 24 to 48 hours. The authors suggested that the results were more than likely due to the inhibition of importin-α/β1– mediated nuclear import of viral proteins, as evidenced in other RNA viruses. Now in vivo studies have commenced in Egypt, Brazil, Iraq and there is at least one U.S. doctor using it as well as evidence from other locations such as the Dominican Republic.
The doctors hypothesize that HCQ and ivermectin could act in a consequential and synergistic manner. Hence, they suggest HCQ could behave as a first-level barrier in its potential ability to inhibit the entry of the virus into the host cell while ivermectin could reduce viral replication if the virus actually does penetrate the first layer.
Some other considerations
HCQ is cheap to make and safe if dosed and monitored properly while Ivermectin appears to be safe and well-tolerated with no serious adverse events according to research they cite published in Actas Dermosifiliogr in 2017.
There have been no studies until now
The doctors acknowledge that their position is just a hypothesis and that there have been no complete in vivo studies.
What are the current studies ongoing using Ivermectin as of May 1, 2020?
The University of Tanta in Egypt now is conducting three clinical trials based on ivermectin as is the University of Baghdad. A French biotech MedinCell also commenced a clinical trials program targeting COVID-19 with Ivermectin. Of course, there is the physician in Broward County who has been treating patients off-label with the drug—the county purportedly signed off on the protocol. And TrialSite News has heard from members of the TrialSite Network worldwide that there are instances where Ivermectin is being used in the fight against COVID-19—but we cannot substantiate those statements.
About the University of Naples, Federico II
Purported to be one of the oldest universities in the world, the institution was founded in 1224. It is now organized in 26 departments and was Europe’s first university to be dedicated to training secular administrative staff. It is the third largest university in Italy by numbers of students enrolled and has a reputation of being one of the better research institutions. It has been ranked among the top 100 universities in the world by citations per paper, achieving a “Very High” ranking for research output by the website Top Universities.
Angela Patri, MD, Dermatology and Venerology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
Gabriella Fabbrocini, MD, MD, Dermatology and Venerology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy