Pharmaceutical and Biomedical Research
Volume:8 Issue: 2, Apr 2022

The coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in late December 2019 and soon became the most serious global health challenge due to the high rate of human-to-human transmission. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and belongs to the large Coronaviridae family [1].

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which has threatened human health and public safety.

Hydroxychloroquine (HCQ) is an anti-malaria drug with controversial antiviral properties. Some in vitro studies have approved its antiviral effects. Many efforts have been made to prevent and treat COVID-19, but effective drugs for complete eradication of COVID-19 have not been found yet and all available drugs are supportive. 

We tried to review some new aspects of HCQ efficacy in the prevention and treatment of COVID-19 infection. Also, some data from recent clinical trials were studied. It has been shown that HCQ may improve some symptoms of patients, but in severe or critical stages, it did not have significant therapeutic effects and did not reduce the rate of mortality.

In this review article, we explained some results of recent studies, including clinical trials on the effects of HCQ on the prevention and treatment of COVID-19 infection. Some studies have revealed HCQ’s beneficial effects in outpatients, and some data showed its hazardous impacts on the heart. The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID. 

It was suggested that the dose of HCQ administration must be adjusted and monitored correctly; furthermore, the levels of some myocardial biomarkers, such as troponin must be measured in mild to moderate, severe, and critical infection. Also, combination therapy with other drugs, such as azithromycin may have better anti-inflammatory and antiviral effects.

The outbreak of severe acute respiratory syndrome coronavirus-2, also called ‘coronavirus disease 2019’ (COVID-19), first appeared in December 2019 in Wuhan, China. COVID-19 is caused by an enveloped single-stranded RNA virus, which has affected more than 14 million people around the world and caused a high rate of mortality. It is notable that discovering new drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is time-consuming. Therefore, reviewing drugs, which have been previously designed for other purposes can be helpful and effective.

Studying the effects of previously approved drugs is important; thus, in this article, we reviewed studies on proposed drugs against COVID-19.

The articles and information were collected from Google Scholar, ScienceDirect, and Scopus databases. We did our research based on keywords, like “therapeutics”, “pharmacology”, “Coronavirus”, “COVID-19”, “SARS”, and “MERS-CoV”. We also applied some filters, such as title/abstract, and ignored factors that could lead to bias and selective selection.

There is currently no cure for coronavirus, and most treatments have been effective to relieve symptoms. The treatment methods and drugs addressed in this article are chosen either from previous drugs against MERS and SARS, drugs that disrupt the life cycle of the coronavirus, or drugs that have been reviewed in retrospective studies and clinical trials.

Prevention and treatment of COVID-19 remain a challenge, in particular for coronavirus and the treatments based on boosting the immune system and preventing virus replication. Epidemiological studies have shown that COVID-19 and SARS-COV transmission are relatively similar. This can help to select the appropriate drug. Thus, anti-inflammatory and antiviral drugs, such as remdesivir are used. Antimalarial drugs, such as hydroxychloroquine (HCQ) and chloroquine (CQ) along with estrogen receptor inhibitors, such as toremifene citrate, which has shown effective results against SARS and MERS, can influence the treatment process. However, more clinical trials are needed to determine the efficacy and side effects of drugs.

Piper chaba Hunter, a flowering vine of the Piperaceae family, has long been used in South Asian countries for culinary purposes and traditionally in fat-rich meat preparation. The curative potential of this herb is of great interest to be studied.

The antioxidant and anticoagulation potential, as well as total phenolic and flavonoid content, were evaluated using cold and boiled water extract separately from the dried and ground stem.

Antioxidant potential was evaluated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and ferric reducing antioxidant power (FRAP) assay. The anticoagulation activity was evaluated by serine protease inhibition assay and prothrombin time (PT) assay. Folin–Ciocalteu (FC) reagent and aluminum complex (AlCl3) were used to assess total phenolic content and total flavonoid content, respectively.

DPPH scavenging assay revealed the IC50 value of 125.52 µg.mL-1 and 157.94 µg.mL-1 for boiled and cold water extract, respectively. Potent ferric reducing potential (FRAP) was observed as 142.87 µM and 135.37 µM of ferrous equivalent per 100 µg for boiled and cold water extract, respectively. The IC50 value of serine protease inhibitory activity was found as 182 µg.mL-1 and 161.12 µg.mL-1 for cold and boiled water extract, respectively. The PT time was 27.00 min for boiled water extract and 24.68 min for cold water extract. Significant phenolic and flavonoid content was also found in the test sample.

P. chaba stem extract possesses potent antioxidant and anticoagulation activity, which can neutralize oxidative free radicals and have a vasodilation effect in oxidative and inflammatory diseases.

Mangrove ecosystems have been recognized to include a wide range of secondary metabolites, which are biochemically distinct, resulting in a diverse range of natural compounds with unique bioactivity. They have active metabolites with new chemical structures from a variety of chemical classes.

This study was undertaken to evaluate the phytochemical screening and cytotoxicity of four major mangrove plants (Excoecaria agallocha L., Acrostichum aureum L., Aegiceras corniculatum L., and Avicennia officinalis L.). 

This experimental study was held in the Biochemistry and Molecular Biology Laboratory of Khulna University, Bangladesh, in 2016. At the first phytochemical screening of the selected plants was observed. Then, the bioactivity as preliminary cytotoxic activity was performed using brine shrimp lethality (BSL) bioassay where a significant 50% Lethal Concentration (LC50) was exerted using polar solvent (ethanol) extract of different plant parts (leaf, bark, and stem). Then, Resazurin Cell Viability Assay was performed only for ethanolic leaf and bark extracts of E. agallocha using four standard bacteria (Escherichia coli ATCC 8739, Salmonella typhi ATCC 6539, Salmonella paratyphi ATCC 9150, and Staphylococcus aureus ATCC 25923).

The experimental findings showed significantly strong LC50 by ethanolic leaf and bark extracts of E. agallocha and other plants, like A. corniculatum, A. aureum, and A. officinalis showed moderate and negligible cytotoxicity, respectively. Then, the experimental findings showed significantly (P≤0.05) strong IC50 by ethanolic leaf and bark extracts of E. agallocha. 

The screens employed in this present study are preliminary and advanced assays are needed to verify and reveal further this bioactivity present in those plants, particularly E. agallocha.

Alzheimer disease is a progressive and irreversible disease that finally leads to death. It destroys cognitive skills and memory, and eventually, the patient cannot do the simplest things.

Cholinesterases (ChEs) which has the capability to control cholinergic transmission would result in elevating acetylcholine levels in the brain, by inhibiting CHEs. Coumarins have been shown to exhibit the inhibitory effect of cholinesterase, where the aromatic component results in designing novel candidates that can inhibit Ab accumulation.

The condensation of aryl aldehydes and 4-hydroxycoumarin. Besides, we applied ZnO nanoparticles as an effective heterogeneous catalyst in [bmim]BF4. To determine the inhibitory activity, we used a substrate, i.e., acetylthiocholine iodide, to assay the tested compounds. Moreover, we applied Ellman’s assay.

The present research is an in vitro work. It explores the possible binding mode of these compounds inside the Acetylcholinesterase (AChE) enzyme. Moreover, regarding the synthesized coumarin derivatives, we also performed docking and Molecular Dynamics (MD) simulation studies. The results indicate a satisfactory inhibitory activity for the assayed compounds against AChE with IC50 values from 0.100 to 0.02 µM. In this sense, the stability of protein-ligand complexes and the interaction of the compounds can be understood by performing a molecular docking with molecular dynamics simulation of 5000 ps in the solvent system for AChE. 

Finally, it is worth mentioning that we also tested coumarin derivatives (L14 and L15), leading to potent and effective AChE inhibitors.

Cardiovascular disease (CVD), especially heart failure (HF) as its common final pathway, is the leading cause of morbidity and mortality worldwide. Furthermore, oxidative and inflammatory processes represent fundamental underlying mechanisms for the development and progression of HF. Of interest, in recent years the development of markers with diagnostic and prognostic value for this pathology and other related CVD has been revalued. 

This study was done to quantify and evaluate inflammatory markers, such as ultra-sensitive C-reactive protein (uCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and heat shock protein 70 (Hsp70) in the serum of patients with HF and to compare them with healthy individuals, also correlate the values obtained from oxidative stress markers and nitric oxide (NO) bioavailability previously investigated in these patients with the coexistence or not of secondary pulmonary hypertension (SPH) associated with HF. 

The determination of all parameters was achieved with standardized, reproducible, accurate, and affordable biochemical methods. 

The values obtained for uCRP, IL-6, and TNF-α were following the pattern of oxidative markers previously found in these patients. These findings indicate the coexistence of oxidative stress and inflammation during HF. Of particular interest, such markers are more exacerbated when were associated with SPH, increasing its value as possible biomarkers in this pathology. However, the found levels of Hsp70 were controversial. 

The pattern of oxidative-inflammatory markers suggests their value as possible biomarkers in this cardiovascular disease. Nevertheless, additional studies are needed to assess in greater detail the importance of the relationship between serum Hsp70 expression and SPH-associated or non-SPH morbidity in HF.

Primordial follicle includes an oocyte surrounded by a layer of somatic cells called Granulosa Cells (GCs). GCs, also known as nurse cells, are an important protective element for the growth and survival of oocytes. Oocytes, which lack some of the metabolic processes, require granulosa cells for their development. 

This manuscript was provided to explain the protocol of GCs primary culture extracted from NMRI mice ovaries.

For choosing the optimum protocol, we used two methods with different culture mediums to obtain more GCs and expedite the process. Hematoxylin and Eosin (H&E) staining and flow cytometry were used to analyze the type of extracted cells from ovaries. Besides, we evaluated the effect of crocin and DPP as two common natural products in Iran on the proliferation of these cells via MTT assay. 

Second protocol method and alpha-MEM culture medium were chosen based on the results. Our findings from HE staining and flow cytometry proved the percentage of cultured GCs in the flask. Further, MTT assessment demonstrated that crocin at high doses had a toxic effect on granulosa cells, whereas date palm pollen (DPP) stimulated them to proliferation. 

Modifying this protocol is for the improvement of proliferation, coherence, and quality of GCs in primary culture and subculture. Regarding the effect of these two natural products on granulosa cells, we can mention the bilateral effect of crocin and DPP enhancement in proliferation.