Infectious Disorders - Drug Targets - Volume 22, Issue 1, 2022

Since the emergence of SARS-CoV-2 in late December 2019, scientists have been racing against time to effectively develop a vaccine. As the techniques of personalized medicine are becoming more understood and approachable for mankind, vaccinations using such technologies could advance the treatment of all patients taking into consideration their genetic and biochemical background. As such, we anticipate that patients will be treated more effectively and potentially have fewer symptoms and side effects. This perspective aims to raise awareness of the oncoming novel treatment of diseases, especially during the coronavirus pandemic.

2019 novel coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 virus, is a member of the family Coronaviridae, which is responsible for the current pandemic of disease COVID-19. It is the seventh member of the family Coronaviridae which infects humans, after 229E, OC43, NL63, HKU1, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Fever, dry cough and severe pneumonia are seen as common symptoms at the early stages of COVID-19. Some cases progress to acute respiratory stress syndrome, septic shock, organ failure, and death. The development of an effective treatment or vaccination for treating or preventing this lethal condition is an urgent need in order to fight this crisis. Up to now, some effective vaccines with different efficacy profiles have been introduced. Herein, we have theoretically designed a scavenger system for gathering 2019-nCoVs, breaking them, and re-introducing them to the immune system.

In the wake of the recent global pandemic of COVID-19, there has been increasing concern among the general public to improve their immune system. The causative agent of COVID-19 is SARS CoV-2, similar to its relative viruses SARS Cov-1 and MERS. Although vaccines have been developed now and are in public use, still the role of a healthy immune system is crucial as new strains of the virus are being discovered and along with emergence of new strains, short and long term side effects of vaccine cannot be excluded. Plants have been used in herbal medicines and many chemicals since ancient times and extracts in them are found to boost the immune system. Therefore, a consciously maintained diet consisting of plant-based immunity boosters is the need of the hour. Plants are known to provide many chemicals, natural therapeutics and vitamins which naturally enhance our immune system. Recently, vaccination research is also being carried out in transgenic plants. In this review, main focus has been put on highlighting some of the key players within the Kingdom Plantae, which, when taken up in regular diet, can significantly boost our immune system capacity and thus helps the human body to combat this deadly virus more efficiently.

SARS-CoV-2 is a novel coronavirus that has been identified, in December 2019, in Wuhan, China, and since it has become a worldwide pandemic, it has imposed far-reaching impacts on global human health and socio-economic activity. Worldwide, over 4 million Covid-19 related deaths were reported until September 2021. Recently published case studies have reported that Covid-19 patients develop different degrees of liver dysfunction. Inevitably, in hospitalized Covid-19 patients who develop acute liver derangement, there are a plethora of potential pathogenic causes such as direct-viral, immune-driven, and drug-induced and/or ischaemic liver injury. Patients with advanced chronic liver diseases (e.g., cirrhosis) and/or autoimmune liver disease have a poor immune function and associated poorer outcomes compared to other critically ill cohorts. However, largely any immediate liver derangement tends to be relatively mild, and as such, any de novo liver injury may not be a significant feature of Covid-19. There is an immediate necessity, therefore, to better understand the liver-specific pathophysiology of COVID-19. This review focuses on the up-to-date information regarding Covid-19 and associated indices for liver dysfunction, possible mechanisms, and potential drug targeted therapies in Covid-19 patients with and without liver dysfunction. PubMed database was used to perform an extensive literature search using the keywords liver and SARS-CoV-2, liver and Covid-19, Covid 19 and treatment, etc.

In late 2019, a report from China was published stating a disease with an unknown cause. After that, the outbreak of the COVID-19 caused a pandemic in the world. On March 11, 2020, the outbreak of this virus was reported in 100 countries.

The virus is currently spreading rapidly around the world. In the past, coronaviruses caused lifethreatening diseases such as SARS and MERS in some areas of the world. Although there is still a debate about the origin of this new coronavirus, it is most likely linked with some animals, including bats, civet, and pangolin. In this review, we try to describe the features of the new coronavirus as well as the recent diagnostic and therapeutic findings.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most infectious diseases which has been caused by coronavirus in 2019 (COVID-19). It has widely spread worldwide and infected more than 28 million people in 215 countries, and more than 920,000 have now died from COVID-19. To date, no effective antiviral drugs or specific vaccines have been discovered yet. Considering this situation, the potential therapeutic antiviral drug targets for the COVID-19 are being repurposed to speed up the discovery of effective treatment. The most potential drug targets that are continuously being recommended include Favipiravir, Chloroquine, Hydroxychloroquine, and Remdesivir. Moreover, the antiviral target proteins and anti-host target proteins are being reported continuously. This review has summarized the current research studies on potential therapeutic drug targets that are being tested against the SARS-CoV-2. It will provide information related to potential repurposing drugs for overcoming COVID-19.

Introduction: COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confront COVID-19. Therefore, we conducted a systematic review to describe the recent treatment strategies to treat COVID-19 patients. Methods: A systematic search was performed in the databases of PubMed, Scopus, Embase, Science direct, Up to date, and Web of Science using the keywords of Coronavirus, COVID-19, SARS-CoV-2, Novel Coronavirus, 2019-nCoV, Treatment, Medicine, Therapy, Intervention, Drug, Medications, and Cure. All the relevant articles were collected from December 2019 to July 2020. Results: We included 58 studies including 38 articles (eleven reviews, ten editorial documents, three case reports, one mix method, one cohort study), and 19 published clinical trials. Review of studies showed that Lopinavir/Ritonavir (n=16), Remdesivir (n=13), Convalescent plasma (n=11), Chloroquine (n=11), Ribavirin (n=9), Hydroxychloroquine sulfate (n=8), Traditional Chinese Medicine (TCM) (n=8), and Arbidol (n=7), were the most frequently therapies used to treat COVID-19 patients. Conclusion: In the absence of definitive treatment protocols, recently proposed approaches have appeared to be an effective therapy for accelerating the recovery of COVID-19 patients. Some of these treatments may have been in the early stages of testing. However, future preclinical and clinical trials are warranted to validate findings.

Background: Previous studies suggested an association between Chlamydia pneumoniae and Mycoplasma pneumonia with atherosclerosis, separately. Until now, according to inconsistent information, the relationship between C.pneumoniae and M.pneumoniae with atherosclerosis is controversial. Objective: The aim of this study is to investigate the association between C.pneumoniae and M.pneumoniae as two separate risk factors with atherosclerosis through systematic review and metaanalysis study. Methods: We searched databases, such as Pubmed, SID, Magiran, Google scholar and Iranmedex, using the following keywords in English and Persian language: C. pneumoniae, M. pneumoniae, and atherosclerosis. Data were analyzed with meta-analysis and a random effect model. Also, in this study, heterogeneity of articles was estimated by using the I2 index. Finally, the data were analyzed with STAT (version 11.2). Results: Among thirty-eight articles for C. pneumoniae and five articles for M. pneumoniae individually reviewed that included 2980 samples for M. pneumoniae and 23298 samples for C. pneumoniae, the result demonstrated that the association between M. pneumoniae and C. pneumoniae with atherosclerosis is significant with OR (odds ratio) = 1.58 (95% Confidence Interval (CI): 1.00 to 2.50), OR (odds ratio) = 2.25 (95% Confidence Interval (CI): 1.91 to 2.64), respectively. Conclusion: This systematic review study provides strong evidence for the role of persistent bacterial infections, such as M. pneumoniae and C. pneumoniae, in potential atherosclerosis. Thus, a novel way should be employed for the complete management of bacterial infection.

Introduction: Tuberculosis (TB) is a serious infectious disease that affects human health globally. The incidence of TB in prisons is usually much higher than the general population in different countries. The aim of this study was to evaluate the incidence of TB among prisoners in Iran, estimating the relative risk factors by performing a systematic and meta-analysis study on the related articles. Methodology: Our systematic and meta-analysis study was performed according to the PRISMA guidelines. Two authors systematically searched Scopus, Iran doc, Cochrane, Pubmed, Medline, Embase, Iran medex, Magiran, SID, Google Scholar, and EBSCO. The quality assessment of articles was performed by using the Newcastle-Ottawa Scale. After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn. Results: Overall, data from 19562 prisoners indicated 63 cases of TB. The prevalence of TB in prisoners was reported to range from 0.025% to 52% in eight studies. The highest prevalence of tuberculosis was related to the study of Rasht, 517 in 100,000, and the lowest rate was related to the study of Sought Khorasan, 25 in 100,000. The ES of the random effect model is 0.003 (95% CI, 0.001-0.005) and p-value <0.0001. The Higgins’ I² of all studies is 86.55%, and the p-value of the Cochrane Q statistics is <0.001, indicating that there is heterogeneity. Based on the Egger regression plot (t=2.18, p = 0.08, CI 95%: -0.001, 0.005), no publication bias existed. Conclusion: According to the analysis findings, the frequency of tuberculosis among the prison in Iran was low. The highest prevalence obtained in our systematic study was 517 in 100,000 in Rasht, which was near the world statistics in the systematic review of world studies. Due to significant limitations in this study, it is not possible to indicate the exact prevalence of TB in prisons in Iran and compare this with the general population. However, more studies are needed to assess the related risk factors for designing health intervention plans to decrease the incidence rate of TB among prisoners.

Introduction: With the increasing rate of COVID-19, particularly in developing countries such as Iran, a high number of frontline service providers, including doctors and nurses, have died, making frontline healthcare workers (HCWs) more vulnerable to psychological disorders and fear and anxiety of secondary transmission to others, especially their family members. In this study, we aimed to report the incidence of COVID-19 infection among HCWs in an Iranian referral pediatrics hospital between April 2020 and July 2020. Materials and Methods: In this retrospective cross-sectional study, HCWs and hospital staff working at Children's Medical Center, Tehran, Iran, with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test results were evaluated between April 2020 and July 2020. Results: Sixty-one out of the 1085 personnel (5.6%) including 14 pediatricians (23%), 24 nurses (39%), 9 paramedics (15%), and 14 HCWs without direct patient contact (23%) had a nasopharyngeal specimen positive SARS-CoV-2 RT-PCR test. The mean age was 39.8±10.6 years. Eleven cases (18%) had underlying diseases such as hypertension and asthma. The most common symptoms were fatigue (67%, n=41), dry cough (61%, n=37), fever (52%, n=32), headache (46%, n=28), dyspnea (43%, n=24), anosmia (28%, n=17), chills (26%, n=16), sore throat (26%, n=16), gastrointestinal symptoms (23%, n=14), and productive cough (3%, n=2). Eleven cases (18%) showed lung involvement in their chest X-rays and/or CT scans. Eighteen cases (29.5%) had lymphopenia, and 20 individuals (33%) had a high level of C-reactive protein. Conclusion: In conclusion, in the early phase of the COVID-19 outbreak, a substantial proportion of HCWs with fever, respiratory, and other prevalent symptoms including fatigue and headache were infected with SARS-CoV-2. Therefore, implementation of infection prevention measures, isolation of confirmed HCWs, disinfection of the environment, and regular COVID-19 prevention training for HCWs are strongly recommended for the wellbeing of health workers and minimizing the spread of infection.

Objective: To evaluate the efficacy of reported anti-malarial phytochemicals as lead compounds for possible drug development against COVID-19. Methods: An in silico approach was used in this study to determine through molecular docking the binding affinities and site of binding of these phytochemicals to the 3C-like protease of COVID-19 which is considered as the main protease of the virus. Results: A number of anti-malarial phytochemicals like apigenin-7-O-glucoside, decurvisine, luteolin- 7-O-glucoside, sargabolide J, and shizukaols A, B, F, and G showed predicted high binding energies with ΔG values of -8.0 kcal/mol or higher. Shizukaols F and B demonstrated the best binding energies of -9.5 and -9.8, respectively. The acridone alkaloid 5-hydroxynoracronycine also gave a predicted high binding energy of -7.9 kcal/mol. Conclusion: This is for the first time that decursivine and several shizukaols were reported as potential anti-viral agents. These compounds merit further studies to determine whether they can be effective drug candidates against COVID-19.

Background: With the growing incidence of microbial pathogenesis, several alternative strategies have been developed. The number of treatments using naturally (e.g., plants, algae, fungi, bacteria, and animals) derived compounds has increased. Importantly, marine-derived products have become a promising and effective approach to combat the antibiotic resistance properties developed by bacterial pathogens. Furthermore, augmenting the sub-inhibitory concentration of the naturally-derived antimicrobial compounds (e.g., hydroxycinnamic acids, terpenes, marine-derived polysaccharides, phenolic compounds) into the naturally derived extracts as a combination therapy to treat the bacterial infection has not been well studied. Objective: The present study was aimed to prepare green algae Ulva lactuca extract and evaluate its antibacterial activity towards Gram-positive and Gram-negative human pathogenic bacteria. Also, revitalize the antibacterial efficiency of the naturally-derived antimicrobial drugs and conventional antibiotics by mixing their sub-MIC to the U. lactuca extracts. Methods: Extraction was done using a different organic solvent, and its antibacterial activity was tested towards Gram-positive and Gram-negative pathogens. The minimum inhibitory concentration (MIC) of U. lactuca extracts has been determined towards pathogenic bacteria using the micro broth dilution method. The viable cell counting method was used to determine the minimum bactericidal concentration (MBC). The fractional inhibitory concentration (FIC) assay was utilized to examine the combinatorial impact of sub-MIC of two antibacterial drugs using the micro broth dilution method. The chemical components of the extract were analyzed by GC-MS analysis. Results: Among all the extracts, n-hexane extract was found to show effective antibacterial activity towards tested pathogens with the lowest MIC and MBC value. Furthermore, the n-hexane extracts have also been used to enhance the efficacy of the naturally-derived (derived from plants and marine organisms) compounds and conventional antibiotics at their sub-inhibitory concentrations. Most of the tested antibiotics and natural drugs at their sub-MIC were found to exhibit synergistic and additive antibacterial activity towards the tested bacterial pathogens. Conclusions: The combining of U. lactuca n-hexane extracts with natural drugs resulted in synergistic and additive bactericidal effects on Gram-positive and Gram-negative human pathogenic bacteria. The present study shows a new alternative strategy to revitalize the antimicrobial activity of naturally derived compounds for treating human bacterial pathogens.

Introduction: SARS-CoV-2 is a novel coronavirus that causes acute respiratory syndrome in humans. It is also known as COVID-19 and was first discovered in Wuhan, Hubei Province in China in December 2019 and soon became a global pandemic. The common symptoms of COVID-19 include fever, fatigue, and dry cough; however, there are some atypical symptoms that remain either unreported or underreported. Case Summary: In this case report, we described a 48-year-old diabetic man who presented with the chief complaint of persistent hiccups (<48h) to the emergency room with no history of malignancy, GI, cardiovascular, or neurological diseases. The patient also mentioned intermittent cough and mild dyspnea initiated the morning of admission day. On physical examination, other than mild tachycardia and tachypnea, there were no notable findings. Following an abnormal chest X-Ray, a chest CT scan was carried out, and peripheral ground-glass opacities along with scattered round opacities were identified in both lungs’ fields. Given the strong suspicion of COVID-19, an RT-PCR test was performed, and the symptomatic treatment was initiated. The patient was diagnosed with COVID-19 following the PCR result release. The treatment was initiated per the protocol, and the patient was transferred to the isolated room and discharged after four days following the relief of the symptoms. Conclusion: It is critical for medical practitioners to seriously consider the possibility of COVID-19 in a patient with similar presentations and isolate the patient at the asymptomatic stages to eliminate the possibility of virus transmission.