Battling COVID-19: using old weapons for a new enemy

Kumar, Rohit; Gupta, Nitin; Kodan, Parul; Mittal, Ankit; Soneja, Manish; Wig, Naveet

doi:10.1186/s40794-020-00107-1

Cited by 23 publications

(21 citation statements)

References 109 publications

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“…Several protease inhibitors designed for other virus families (e.g., HIV), exhibited in vitro activity against SARS-CoV and MERS-CoV, thus application for SARS-CoV-2 appears reasonable [ 74 , 75 ]. In this category of active compounds, lopinavir and ritonavir are currently listed as the most promising candidates [ 76 ].…”

Section: Current Therapeutic Targetsmentioning

confidence: 99%

“…In consequence, lopinavir (ABT-378) was developed as a way out, possessing a diminished interaction with the mutation site of HIV protease [ 77 ]. Both lopinavir and ritonavir, are currently approved as a combination therapy of HIV infections, where ritonavir inhibits CYP3A4 even in subtherapeutic dosage, resulting in higher plasma concentrations of lopinavir [ 34 , 75 , 76 ]. The inhibition of HIV protease results in the formation of immature virions and renders them noninfectious [ 76 ].…”

Section: Current Therapeutic Targetsmentioning

confidence: 99%

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COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

Blaess

Kaiser

Sauer

et al. 2020

IJMS

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In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.

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Section: Current Therapeutic Targetsmentioning

confidence: 99%

Section: Current Therapeutic Targetsmentioning

confidence: 99%

COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

Blaess

Kaiser

Sauer

et al. 2020

IJMS

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“…CD147 can also bind to the spike protein of SARS-CoV-2 for entry into the host cell [ 11 , 38 ]. Targeting of CD147 through the meplazumab monoclonal antibody could be a possible potential therapy against COVID-19 disease (Table 1 ) [ 96 ].…”

Section: Potential Colliding Targets and Associated Drugsmentioning

confidence: 99%

“…Targeting of CD147 through the meplazumab monoclonal antibody could be a possible potential therapy against COVID-19 disease (Table 1 ) [ 96 ].…”

Section: Potential Colliding Targets and Associated Drugsmentioning

confidence: 99%

Impact of Gastrointestinal Symptoms in COVID-19: a Molecular Approach

Sonkar

Kashyap

Varshney

et al. 2020

SN Compr. Clin. Med.

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The pandemic of novel coronavirus disease (COVID-19) caused by the Severe Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) creates an immense menace to public health worldwide. Currently, the World Health Organization (WHO) has recognized the novel coronavirus as the main cause of global pandemic. Patients infected with this virus generally show fever, nausea, and respiratory illness, while some patients also manifest gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea. Traces of SARS-CoV-2 RNA have been found in gastrointestinal cells. Further angiotensin converting enzyme 2 (ACE2) the known receptor for the virus is extensively expressed in these cells. This implies that gastrointestinal tract can be infected and can also present them as a replication site for SARS-CoV-2, but since this infection may lead to multiple organ failure, therefore identification of another receptor is a plausible choice. This review aims to provide comprehensive information about probable receptors such as sialic acid and CD147 which may facilitate the virus entry. Several potential targets are mentioned which can be used as a therapeutic approach for COVID-19 and associated GI disorders. The gut microbiomes are responsible for high levels of interferon-gamma which causes hyper-inflammation and exacerbates the severity of the disease. Briefly, this article highlights the gut microbiome’s relation and provides potential diagnostic approaches like RDT and LC-MS for sensitive and specific identification of viral proteins. Altogether, this article reviews epidemiology, probable receptors and put forward the tentative ideas of the therapeutic targets and diagnostic methods for COVID-19 with gastrointestinal aspect of disease.

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“…Inosine might also exert antiviral effects through the incorporation into double-stranded viral RNA and potentiation of immune system sensing ( Sarvestani et al 2014 ). It is important to note here that inosine-based compounds are amongst the drugs that being re-purposed for management of Covid-19 ( Kumar et al 2020 ), and the efficacy of high-dose glutathione therapy in relieving dyspnea associated with Covid-19 pneumonia has been recently reported ( Horowitz et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis-based pre-exposure prophylaxis associated with low risk of SARS-CoV-2 infection in healthcare workers at a designated Covid-19 hospital

Dubina

Gomonova

Тараскина

et al. 2020

Preprint

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At present, no agents are known to be effective in preventing Covid-19. Based on current knowledge of the pathogenesis of this disease, we suggest that SARS-CoV-2 infection might be attenuated by directly maintaining innate pulmonary redox, metabolic and dilation functions using well-tolerated medications that are known to serve these functions, specifically, using a low dose aerosolized combination of glutathione, inosine and potassium. From June 1 to July 10, 2020, we conducted a low-intervention open-label single-centre study to evaluate safety and efficacy of pre-exposure prophylaxis (PrEP) with the aerosolized combination medications (ACM) on SARS-CoV-2 incidence in 99 healthcare workers (HCWs) at a hospital that was designated to treat Covid-19 patients. We also retrospectively compared SARS-CoV-2 incidence in the ACM users to that in 268 untreated HCWs at the same hospital. Eligible participants received an aerosolized combination of 21.3 mg/ml glutathione, 8.7 mg/ml inosine in 107 mM potassium solution for 14 days. The main outcome was the frequency of laboratory confirmed SARS-CoV-2 cases, defined as individuals with positive genetic or immunological tests within 28 days of the study period. During the PrEP period, solicited adverse events occurred in five participants; all were mild and transient reactions. SARS-CoV-2 was detected in 2 ACM users (2%, 95% CI: 0.3% to 7.1%), which was significantly less than the incidence in 24 nonusers (9%, 95% CI: 5.8% to 13.0%; P = 0.02). Our findings might be used either to prevent SARS-CoV-2 infection, or to support ongoing and new research into more effective treatments for Covid-19.

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Battling COVID-19: using old weapons for a new enemy

Cited by 23 publications

References 109 publications

COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

Impact of Gastrointestinal Symptoms in COVID-19: a Molecular Approach

Pathogenesis-based pre-exposure prophylaxis associated with low risk of SARS-CoV-2 infection in healthcare workers at a designated Covid-19 hospital

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