Targeting COVID-19 in Parkinson’s Patients: Drugs Repurposed

Abstract

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

Characteristics and Outcomes of Parkinson's Disease Individuals Hospitalized with COVID‐19 in a New York City Hospital System

“… 21 Amantadine interferes with viroporin protein channel involved in the release of RNA in SARS coronavirus and potential mechanisms have been proposed for reduction of the viral load and severity of the disease in PD patients. 22 A comprehensive assessment of comorbidities associated with severity and prognosis of COVID‐19 showed chronic kidney disease, chronic obstructive pulmonary disease (COPD), and hypertension are major factors that contribute to increased disease severity and worse prognosis. 23 In our cohort, none of the measured comorbidities had a significant effect on mortality, possibly because of insufficient power to detect differences.…”

“…There are several hypotheses with regard to the potential therapeutic role of PD medications in COVID because of possible co‐expression of dopa decarboxylase, and angiotensin‐converting enzyme 2, the main receptor to SARS‐CoV2 21 . Amantadine interferes with viroporin protein channel involved in the release of RNA in SARS coronavirus and potential mechanisms have been proposed for reduction of the viral load and severity of the disease in PD patients 22 . A comprehensive assessment of comorbidities associated with severity and prognosis of COVID‐19 showed chronic kidney disease, chronic obstructive pulmonary disease (COPD), and hypertension are major factors that contribute to increased disease severity and worse prognosis 23 .…”

COVID-19 and neurological disorders: what might connect Parkinson’s disease to SARS-CoV-2 infection

“…Moreover, it must be considered that generally dopamine agonists are used in the initial or mild stages of the disease, therefore in patients less advanced in the natural history of PD. Also, amantadine, an anti-viral drug used to treat levodopa-induced dyskinesia has been hypothesizing to disrupt the lysosomal machinery needed for SARS-CoV-2 replication or to block the viroporine channel of SARS-CoV-2 preventing the release of the viral nucleus into cells ( 58 , 59 , 61 ). Accordingly, to these hypotheses, several studies has been published indicating the potential role of amantadine in the prevention of the clinical symptoms related to COVID-19 ( 68 , 72 ).…”

Management of Parkinson’s Disease in the COVID-19 Pandemic and Future Perspectives in the Era of Vaccination

“…33,34 Amantadine, which is commonly used in PD, has been repurposed to treat COVID-19, as it plays a potential role as an antiviral agent against SARS-CoV-2 by blocking the matrix-2 (M2) protein ion channel and disrupting lysosomal gene expression to reduce viral replication. 22,33,35 Antivirals, such as favipiravir, atazanavir, and lopinavir/ritonavir, and antimalarial agents, such as chloroquine and hydroxychloroquine, are being tested for CO-VID-19, and thus far, no specific interactions with dopaminergic medications have been reported. 23 A high index of suspicion is necessary, especially if patients present with acute deterioration in their motor symptoms.…”

“…Postviral parkinsonism, which has been described historically as encephalitis lethargica, can occur either immediately or much later following an acute episode of viral illness. 9,[35][36][37] Clinical presentations typically involve upper limb bradykinesia and stiffness associated with frequent episodes of kinesia paradoxica, oculogyric crisis, and psychiatric symptoms. Encephalitis lethargica could be just a contributing factor rather than a prerequisite to developing postencephalitic parkinsonism.…”