Treatment Of COVID-19 Disease Research Articles

It is time to drop hydroxychloroquine from our COVID-19 armamentarium

Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.

Tratamiento farmacológico en tiempos de incertidumbre: uso de la hidroxicloroquina/cloroquina en el tratamiento de COVID-19

Background and objectives: In this moments, of extreme gravity in which we find ourselves, and in the uncertainty face about the most effective treatment against COVID-19 disease and with the aim of find the evidence that support the chloroquine/hydroxychloroquine use recommendation to treat COVID-19 disease, a systematic review of published studies and RCT studies publishes until April 28, 2020 was carried out. Material and methodsA systematic search was carried out in PubMed with the keywords COVID-19 and their synonyms and hydroxychloroquine/chloroquine. The data selection and extraction was elaborated by two researchers, independently. The results were discussed with a Primary Care physicians clinical group and the results were synthesized using GRADE methodology. ResultsA good quality systematic review was found that includes articles with a high risk of bias. And 8 EC launched that will produce results beyond May 2020. ConclusionsAlthough the conclusions of the systematic review generate a low confidence in the results, and the clinical variables that show benefit are intermediate variables, the side effects are acceptable and could be minimized with the use of QT lengthening risk tools, so it is could make a weak recommendation in favor of the use of chloroquine/hydroxychloroquine in patients with mild-moderate stage COVID-19.

Why the lower reported prevalence of asthma in patients diagnosed with COVID-19 validates repurposing EDTA solutions to prevent and manage treat COVID-19 disease

There currently is no specific antiviral drug or a vaccine for SARS-CoV-2/COVID-19 infections; now exceeding 10,300,000 infections worldwide. In the absence of animal models to test drugs, we need to find molecular explanations for any unforeseen peculiarities in clinical data, especially the recent reports describing an unexpected asthma paradox. Asthma is considered a high medical risk factor for susceptibility to SARS-CoV-2/COVID-19 infection, yet asthma is not on the list of top 10 chronic health problems suffered by people who died from SARS-CoV-2/COVID-19. Resolving this paradox requires looking beyond the binary model of a viral receptor-binding domain (RBD) attaching to the ACE-2 receptor. A NCBI pBlast analysis revealed that the SARS-CoV-2 surface spike protein contains key two calcium-dependent fusion domains that are almost identical to those that were recently discovered SARS-CoV-1. These viral calcium-dependent binding domains can facilitate membrane fusion only after cleavage by the host surface protease TMPRSS2. Importantly, TMPRSS2 also requires calcium for its SRCR (scavenger receptor cysteine-rich) domain and itsLDLRA(LDL receptor class A) domain. Thus, the presence of EDTA excipients in nebulized β2-agonist medicines can disrupt SARS-CoV-2/COVID-19 infection and can explain the asthma paradox. This model validates repurposing EDTA in nebulizer solutions from a passive excipient to an active drug for treating COVID-19 infections. Repurposed EDTA delivery to respiratory tissues at an initial target dose of 2.4 mg per aerosol treatment is readily achievable with standard nebulizer and mechanical ventilator equipment. EDTA warrants further investigation as a potential treatment for SARS-CoV-2/COVID-19 in consideration of the new calcium requirements for virus infection and the regular presence of EDTA excipients in common asthma medications such as Metaproterenol. Finally, the natural history of Coronavirus diseases and further analysis of the fusion loop homologies between the Betacorona SARS-CoV-2 virus and the less pathogenic Alphacorona HC0V-229E virus suggest how to engineer a hybrid virus suitable for an attenuated alpha-beta SARS-CoV-2/COVID-19 vaccine. Thus, replacing SARS-CoV-2 fusion loops (amino acids 816–855) with the less pathogenic HCoV-229E fusion loop (amino acids 923–982) may provide antigenicity of COVID-19, but limit the pathogenicity to the level of HCoV-229E.

The virtual screening application for searching potential antiviral agents to treat COVID-19 disease

Aim. To provide a brief literature review regarding the structure of the human coronavirus SARS-CoV-2, the mechanism of its replication and the role of viral proteases in this process; to analyze the ability of the known antiviral agents and compounds synthesized de novo in order to bind and inhibit the coronavirus main protease using computer simulation tools.Results and discussion. COVID-19 coronavirus has become a worldwide challenge in recent months. Taking into account the rapid spread and severity of COVID-19 among a significant part of the population there is an urgent need to develop effective medicines and appropriate treatment protocols, which, unfortunately, are not yet available. Currently, the search for molecules with an acceptable toxicity profile that are able to inhibit and/or stop coronavirus SARS-CoV-2 replication in the human body is very relevant. In this study, the virtual screening and molecular docking of both antiviral agents known and new compounds synthesized have been performed based on the structure of the main protease Mpro of SARS-CoV-2. The regularities identified during our study can be useful for searching and developing new antiviral drugs to control COVID-19 and other coronavirus infections. The analysis of the results of calculations of physicochemical characteristics of antiviral agents, as well as the determination of their binding sites with the main viral protease Mpro gives an optimistic assessment of the possibility to develop new drugs based on the structures of the known antiviral drugs or their modified analogs.Experimental part. Based on recent studies of the crystal structure of the virus main protease Mpro in the complex with various inhibitors (Protein Data Bank http://www.rcsb.org/pdb, the structure code – 6LU7) the virtual screening and molecular docking of 100 known antiviral agents and 50 novel compounds synthesized were performed. The screening data for the in vitro antimalarial activity of the compounds synthesized were presented. The following binding and physicochemical parameters of the ligand–protein interaction for all virus main protease potential inhibitors were calculated: binding affinity score (BAS), binding energy, lipophilicity (clogP) and topological polar surface area (TPSA). The protein and ligand structures were studied using Jmol, PyMol, and Avogadro graphics software packages. The virtual screening and molecular docking, as well as the analysis of the results were performed using a LigandScout 4.4 software package. Data on the antimalarial activity of 50 compounds synthesized were obtained from the Laboratory of Microbiology, Parasitology and Hygiene of theUniversity ofAntwerp (Belgium).Conclusions. According to the results of the virtual screening and molecular docking with protein 6LU7 it has been found that a number of the known antiviral drugs have a certain potential for their use as inhibitors of SARS-CoV-2 coronavirus main protease. Remdesivir and ritonavir substances have shown higher activity than the reference compound of the 6LU7 complex. The molecular docking of a series of compounds recently synthesized with the proven in vitro antimalarial activity has revealed that L1 – L6 compounds are promising candidates for further modification and development of new antiviral drugs to control coronavirus infection.Received: 02.04.2020Revised: 23.05.2020Accepted: 29.05.2020

COVID-19 and heme oxygenase: novel insight into the disease and potential therapies.

The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19’s heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection’s damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19.

The coronavirus, COVID-19, has infected hundreds of thousands and killed tens of thousands of individuals worldwide. This highly infectious condition continues to ravage the world population and has yet to reach it peak infective rate in some countries. Many conventional drugs including hydroxychloroquine/chloroquine, lopinavir, remdesivir, etc., have been repurposed as treatments for this often deadly disease, but there is no specifically-designed effective drug available; also, the drugs mentioned have significant side effects and their efficacy is unknown. New drugs and vaccines are being designed as COVID-19 treatment, but their development and testing will require months to years. Time is not a luxury that this crisis has. Thus, there is a serious unmet need for the identification of currently-available and safe molecules which can be used to slow or treat COVID-19 disease. Here, we suggest melatonin be given consideration for prophylactic use or treatment alone or in combination with other drugs. Melatonin's multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) make it a reasonable choice for use. Melatonin is readily available, can be easily synthesized in large quantities, is inexpensive, has a very high safety profile and can be easily self-administered. Melatonin is endogenously-produced molecule in small amounts with its production diminishing with increased age. Under the current critical conditions, large doses of melatonin alone or in combination with currently-recommended drugs, e.g., hydroxychloroquine/chloroquine, to resist COVID-19 infection would seem judicious.

The-convalescent-serum-for-treatment-of-covid-19-infection-review

In the early of 2020, people are challenging a pandemic in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 causes coronavirus disease, abbreviated as COVID-19. At the time of this writing, SARS-CoV-2 is spreading in multiple countries worldwide. There are above two million cases in different region of world. This virus appears to be a new human pathogen. Currently there are no vaccines, monoclonal antibodies (mAbs), or drugs available for SARS-CoV-2, though many are in rapid development and some may be accessible in a short time. This aim of this review that human convalescent serum is an option for stoppage and treatment of COVID-19 disease. Explain main advantage of convalescent serum, in addition to disadvantage of this method.

Drug repositioning is an alternative for the treatment of coronavirus COVID-19

Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.

Acute respiratory distress syndrome in COVID-19

Emerging coronavirus-related respiratory disease started from Wuhan, China in December 2019 resulted in numerous mortality following acute respiratory distress syndrome (ARDS) named COVID-19 disease. The incubation period of COVID-19 is varied from 2 days to 2 weeks; therefore oral transmission is the most hazardous issue in this incubation period. Scientists are trying to find a specific drug to treat COVID-19 disease, however there is no specific therapy yet. One of the challenging issues in the treatment process of these patients is ARDS. In the development of any type of pneumonia or ARDS, Covid-19 should be considered as an option for differential diagnosis and the first critical organ in these patients is lung. In this paper, we discussed ARDS in patients with COVID-19.

Assessment of Corona in Pregnant Women: Epidemiology, Clinical Signs, Prevention and Treatment

Coronaviruses are considered as viruses causing disease in humans and some animals. Some coronaviruses have mild symptoms similar to colds. On the other hand, some of them lead to acute respiratory complications. The new coronavirus known as Covid-19 is a seriously contagious viral disease infecting more than 10 million people during 6 months. This virus has signs close to SARS and this similarity led to public health hazard. There is a serious concern about pregnant women and their infants infected with this virus. Therefore, a lot of cares should be taken for these women during pregnancy and afterwards by obstetricians, nurses, and their close relatives. Findings indicated a possible vertical transmission of Coronavirus to the fetus through the placenta, but there is not any document confirming this report. This study reviews epidemiology, transmission, clinical signs, prevention, and treatment of Covid-19 disease with respect to the importance of pregnant mothers' health and coronal virus complications.

Clinical Characteristics and Report of Seven Iranian Neonates Born to Mothers with Covid-19

The outbreak of Covid-19 infection is an actual public health challenge. Iran is fighting hard against the virus outbreak. Although at first it seemed that the disease does not affect infants and the neonates, But the population of affected infants and neonates appears to be increasing. This article is written to share some of the experiences about encountering with neonates born to mothers with covid-19. It describes the maternal, perinatal and neonatal aspects of the disease in seven Iranian cases. It also explains the outcome of delivery and follow up of mothers and their neonates after they discharged from hospital. According to our vague and incomplete knowledge about this novel disease and also hazardous side effects of its specific drugs which are not fully evaluated in neonatal population, in this article we just emphasize on routine and supportive care and avoiding unconventional therapy. In this case series we manage our patients according to their disease such as pneumonia, transient tachypnea of neonates or respiratory distress syndrome by using antibiotics, total parenteral nutrition and supplementary oxygen therapy with the preference of non-invasive methods. We didn’t use any novel treatment for Covid-19 disease. We also carefully considered isolation and personal protection issues.