Therapeutic Management of COVID-19 Patients

Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCov-2) or COVID-19 is a pandemic that appeared in December 2019 in China and which is an RNA virus. It gave rise to a major health crisis at the start of 2020, with numerous hospitalizations. It was quickly important to understand the pathophysiology of this viral attack on the human body in order to be able to develop treatment. However, there is no vaccine or effective therapeutic agent against SARS-CoV-2. Most of the therapeutic strategies used to deal with this virus come from the work of previous epidemics of SARS, and other influenza viruses, such as antiviral therapies (chloroquine, hydroxychloroquine), adjuvant therapies by combining antivirals with drugs. Antibiotics or immunostimulants (vitamins C, Dm and Zinc, etc,) and several other therapies to be used depending on the region.

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Role of Endolysosomes in Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Coronavirus Disease 2019 Pathogenesis: Implications for Potential Treatments

Frontiers in Pharmacology ◽

10.3389/fphar.2020.595888 ◽

2020 ◽

Vol 11 ◽

Author(s):

Nabab Khan ◽

Xuesong Chen ◽

Jonathan D. Geiger

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Rna Virus ◽

Therapeutic Strategies ◽

Host Protein ◽

Focus Attention ◽

Angiotensin Converting Enzyme 2 ◽

Immunological Responses ◽

Endocytic Machinery ◽

Replication Sites

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis.

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Instability of Nucleic Acids in Airborne Microorganisms under Far Infrared Radiation

10.20944/preprints202002.0332.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Wei-Hong Huang ◽

En-Jing Li

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Rna Virus ◽

Virus Transmission ◽

Far Infrared ◽

Influenza Viruses ◽

Airborne Particles ◽

Human Pathogens ◽

Airborne Microorganisms ◽

Far Infrared Radiation

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, Wuhan coronavirus (COVID-19), plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms were stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission and cure RNA virus infection were proposed, implying that FIR radiation might be a cheap, convenient, and efficient method in clinic to treat RNA virus.

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Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽

10.3390/v13050774 ◽

2021 ◽

Vol 13 (5) ◽

pp. 774

Author(s):

Chengfeng Gao ◽

Chunxia Wen ◽

Zhifeng Li ◽

Shuhan Lin ◽

Shu Gao ◽

...

Keyword(s):

Broad Spectrum ◽

Zika Virus ◽

Therapeutic Agent ◽

Viral Infections ◽

Rna Virus ◽

Emerging Viruses ◽

Enterovirus A71 ◽

Ic50 Values ◽

High Doses ◽

Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

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COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Biomolecules ◽

10.3390/biom11070993 ◽

2021 ◽

Vol 11 (7) ◽

pp. 993

Author(s):

Renuka Raman ◽

Krishna J. Patel ◽

Kishu Ranjan

Keyword(s):

Immune Response ◽

Monoclonal Antibodies ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Viral Vector ◽

Therapeutic Strategies ◽

Convincing Evidence ◽

Plasma Therapy ◽

Therapeutic Monoclonal Antibodies ◽

Increased Susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13123026 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3026

Author(s):

Hyuk Moon ◽

Simon-Weonsang Ro

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Therapeutic Strategies ◽

Erk Signaling ◽

Health Concern ◽

Alternative Mechanism ◽

Major Health ◽

Activating Mutations ◽

Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

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CASE SERIES: A SPECTRUM OF FUNGAL INFECTIONS IN COVID-19

10.36106/ijsr/8120981 ◽

2021 ◽

pp. 29-30

Author(s):

Venkatesh B. C. ◽

Rajendra Rao K. M. ◽

K. N. Mohan Rao

Keyword(s):

Diabetes Mellitus ◽

Fungal Infections ◽

Virus Disease ◽

Case Series ◽

Health Crisis ◽

Major Health ◽

Corona Virus ◽

Patients With Diabetes ◽

Causative Agents

Corona virus Disease 2019 (COVID-19) pandemic is causing a major health crisis across the globe. With the increasing number of fungal infections associated with COVID-19 being reported, it is imperative to understand the spectrum of such infections. Most documented cases have been reported in patients with diabetes mellitus or treatment with immunomodulators. The most common causative agents are Aspergillus, Candida or Mucorales. This series aims to portray the spectrum of fungal infections associated with COVID-19.

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Hepatitis B virus: from immunobiology to immunotherapy

Clinical Science ◽

10.1042/cs20120169 ◽

2012 ◽

Vol 124 (2) ◽

pp. 77-85 ◽

Cited By ~ 20

Author(s):

Daniel Grimm ◽

Maximilian Heeg ◽

Robert Thimme

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Therapeutic Approaches ◽

Major Health ◽

Antiviral Therapies ◽

Adaptive Immune ◽

Host Interaction ◽

Current State ◽

B Virus ◽

Chronic Hbv

Owing to the major limitations of current antiviral therapies in HBV (hepatitis B virus) infection, there is a strong need for novel therapeutic approaches to this major health burden. Stimulation of the host's innate and adaptive immune responses in a way that results in the resolution of viral infection is a promising approach. A better understanding of the virus–host interaction in acute and chronic HBV infection revealed several possible novel targets for antiviral immunotherapy. In the present review, we will discuss the current state of the art in HBV immunology and illustrate how control of infection could be achieved by immunotherapeutic interventions.

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Development of a Colloidal Gold-Based Immunochromatographic Strip for Rapid Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein

Frontiers in Immunology ◽

10.3389/fimmu.2021.635677 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ge Li ◽

Aiping Wang ◽

Yumei Chen ◽

Yaning Sun ◽

Yongkun Du ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Colloidal Gold ◽

Global Economy ◽

Chinese Hamster ◽

Influenza Viruses ◽

Spike Protein ◽

Disease Spread ◽

Ovary Cell ◽

Immunochromatographic Strip ◽

Specific Reactions

The outbreak and worldwide pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a significant impact on global economy and human health. In order to reduce the disease spread, 16 monoclonal antibodies (McAbs) again SARS-CoV-2 were generated by immunized mice with the spike protein receptor binding domain (RBD), which was expressed in Chinese hamster ovary cell (CHO). A colloidal gold-based immunochromatographic strip was developed with two McAbs to detect SARS-CoV-2 spike protein, which can play a potential role in monitoring vaccine quality. The strip is highly specific, detecting only SARS-CoV-2 spike protein, and does not show any non-specific reactions with syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and other coronavirus and influenza viruses. The strip detected subunit vaccine in our laboratory with a detection limit of spike protein of 62.5 ng/mL. This strip provides an effective method in monitoring vaccine quality by detecting the antigen content of spike protein.

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Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Česká a slovenská farmacie ◽

10.5817/csf2021-1-18 ◽

2021 ◽

Vol 70 (1) ◽

pp. 18-25

Author(s):

Malík Ivan ◽

Čižmárik Jozef ◽

Kováč Gustáv ◽

Pecháčová Mária ◽

Hudecová Lucia

Keyword(s):

Influenza Virus ◽

Severe Acute Respiratory Syndrome ◽

Rift Valley Fever Virus ◽

Encephalitis Virus ◽

Influenza Viruses ◽

Swine Flu ◽

Influenza B Virus ◽

Influenza B ◽

Antiviral Compound ◽

Virus Influenza

Since the beginning of the outbreak, a large number of clinical trials have been registered worldwide, and thousands of drugs have been investigated to face new health emergency of highly contagious COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Drug repurposing, i.e., utilizing an approved drug for a different indication, offers a time- and cost-efficient alternative for making new (relevant) therapies available to physicians and patients. Considering given strategy, many approved and investigational antiviral compounds, alone or in various relevant combinations, used in the past to fight Severe Acute Respiratory Syndrome Coronavirus-1, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus type 1, or Influenza viruses are being evaluated against the SARS-CoV-2. Triazavirin (TZV), a non-toxic broad--spectrum antiviral compound, is efficient against various strains of the Influenza A virus (Influenza Virus A, Orthomyxoviridae), i.e., swine flu (H1N1, or H3N2), avian influenza (H5N1, H5N2, H9N2, or highly pathogenic H7N3 strain), Influenza B virus (Influenza Virus B, Orthomyxoviridae), Respiratory Syncytial Virus (Orthopneumovirus, Pneumoviridae), Tick-Borne Encephalitis Virus (known as Forest-Spring Encephalitis Virus; Flavivirus, Flaviviridae), West Nile Virus (Flavivirus, Flavaviridae), Rift Valley Fever Virus (Phlebovirus, Bunyaviridae), and Herpes viruses (Simplexviruses, Herpesviridae) as well. In regard to COVID-19, the molecule probably reduced inflammatory reactions, thus limiting the damage to vital organs and reducing the need for therapeutic support, respectively. In addition, in silico computational methods indicated relatively satisfactory binding affinities of the TZV ligand to both structural (E)- and (S)-proteins, non-structural 3-chymotrypsin-like protease (3-CLpro) of SARS-CoV-2 as well as human angiotensin-I converting enzyme-2 (ACE-2). The interactions between TZV and given viral structures or the ACE-2 receptor for SARS-CoV-2 might effectively block both the entry of the pathogen into a host cell and its replication. Promising treatment patterns of COVID-19 positive patients might be also based on a suitable combination of a membrane fusion inhibitor (umifenovir, for example) with viral RNA synthesis and replication inhibitor (TZV).

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Interaction of serum proteins with SARS-CoV-2 RBD

Nanoscale ◽

10.1039/d1nr02687a ◽

2021 ◽

Author(s):

Yue-wen Yin ◽

Yan-jing Sheng ◽

Min Wang ◽

Yu-qiang Ma ◽

Hong-ming Ding

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Serum Proteins ◽

Biological Fluids ◽

Health Crisis ◽

Public Health Crisis

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids...

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