Repurposing of antiviral drugs for COVID-19 and impact of repurposed drugs on the nervous system

Punekar, Madhura; Kshirsagar, Manas; Tellapragada, Chaitanya; Patil, Kanchankumar

doi:10.1016/j.micpath.2022.105608

Cited by 13 publications

(6 citation statements)

References 111 publications

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“…For example, oseltamivir has been documented to be related to neurological toxicity ( Ono et al, 2018 ). A large-scale analysis of data from the US Food and Drug Administration Adverse Event Reporting System reported neuropsychiatric adverse events associated with treatment with oseltamivir in cases of SARS-CoV-2 infection, which were described as abnormal behavior, hallucinations, and seizures ( Punekar et al, 2022 ). Oseltamivir has limited penetration through the BBB because it is a P-glycoprotein substrate ( DrugBank, 2022 ).…”

Section: Modification In Drug Transport Through the Bbb Altered By Sa...mentioning

confidence: 99%

Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain

Hernández-Parra

Reyes-Hernández²,

Figueroa‐González³

et al. 2023

Front. Cell. Neurosci.

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Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms “COVID-19” or “SARS-CoV-2” and “blood-brain barrier injury” or “brain injury” from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1β, IL-6, TNF-α, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs’ beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters.

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Section: Modification In Drug Transport Through the Bbb Altered By Sa...mentioning

confidence: 99%

Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain

Hernández-Parra

Reyes-Hernández²,

Figueroa‐González³

et al. 2023

Front. Cell. Neurosci.

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“…Repurposing antivirals is an effective method to control outbreaks more rapidly, reducing costs in research and reducing the risk of failure or adverse effects [ 156 ]. There are many drugs that have been approved to be used for the treatment of COVID-19; however, most of them have been repurposed and were not designed for this use.…”

Section: Available and Alternative Treatments/prophylaxismentioning

confidence: 99%

Antivirals for Broader Coverage against Human Coronaviruses

Outteridge,

Nunn,

Devine

et al. 2024

Viruses

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Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27–31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are seven known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2, responsible for the COVID-19 pandemic. Antivirals that have been approved by the FDA for use against COVID-19 such as Paxlovid can target and successfully inhibit the main protease (MPro) activity of multiple human CoVs; however, alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak but also the four common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, could target other CoVs, but only SARS-CoV-2 is known to be targeted in vivo. Other drugs which have the potential to target other human CoVs are still within clinical trials and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates; however, they target the Spike protein whose sequence mutates frequently and drifts. Spike is also not applicable for targeting other HCoVs as these are not well-conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all seven human CoVs and improve the preparedness for inevitable future outbreaks. Here, we discuss antiviral research, contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future.

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“…The urgent need to reduce COVID-19 severity and related mortality prompted the massive repurposing of approved antivirals in efforts to use them against SARS-CoV-2. However, this approach has had limited success ( Martinez, 2022 ; Punekar et al., 2022 ). The major medical impact of the SARS-CoV-2 pandemic made it an obvious research priority to develop new and effective broad-spectrum antivirals that suppress critical phases of the viral replication cycle.…”

Section: Introductionmentioning

confidence: 99%

Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation

et al. 2023

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Repurposing of antiviral drugs for COVID-19 and impact of repurposed drugs on the nervous system

Cited by 13 publications

References 111 publications

Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain

Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain

Antivirals for Broader Coverage against Human Coronaviruses

Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation

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