Detection of Adverse Drug Reactions in COVID-19 Hospitalized Patients in Saudi Arabia: A Retrospective Study by ADR Prompt Indicators

Seeking an alternative approach for detecting adverse drug reactions (ADRs) in coronavirus patients (COVID-19) and enhancing drug safety, a retrospective study of six months was conducted utilizing an electronic medical record (EMR) database to detect ADRs in hospitalized patients for COVID-19, using "ADR prompt indicators” (APIs). Consequently, confirmed ADRs were subjected to multifaceted analyses, such as demographic attribution, relationship with specific drugs and implication for organs and systems of the body, incidence rate, type, severity, and preventability of ADR. The incidence rate of ADRs is 37%, the predisposition of organs and systems to ADR is observed remarkably in the hepatobiliary and gastrointestinal systems at 41.8% vs. 36.2%, p < 0.0001, and the classes of drugs implicated in the ADRs are lopinavir-ritonavir 16.3%, antibiotics 24.1%, and hydroxychloroquine12.8%. Furthermore, the duration of hospitalization and polypharmacy are significantly higher in patients with ADRs at 14.13 ± 7.87 versus 9.55 ± 7.90, p < 0.001, and 9.74 ± 5.51 versus 6.98 ± 4.36, p < 0.0001, respectively. Comorbidities are detected in 42.5% of patients and 75.2%, of patients with DM, and HTN, displaying significant ADRs, p-value < 0.05. This is a symbolic study providing a comprehensive acquaintance of the importance of APIs in detecting hospitalized ADRs, revealing increased detection rates and robust assertive values with insignificant costs, incorporating the hospital EMR database, and enhancing transparency and time effectiveness.

Detection of Adverse Drug Reactions in COVID-19 Hospitalized Patients in Saudi Arabia: A Retrospective Study by ADR Prompt Indicators.

Seeking an alternative approach for detecting adverse drug reactions (ADRs) in coronavirus patients (COVID-19) and enhancing drug safety, a retrospective study of six months was conducted utilizing an electronic medical record (EMR) database to detect ADRs in hospitalized patients for COVID-19, using "ADR prompt indicators" (APIs). Consequently, confirmed ADRs were subjected to multifaceted analyses, such as demographic attribution, relationship with specific drugs and implication for organs and systems of the body, incidence rate, type, severity, and preventability of ADR. The incidence rate of ADRs is 37%, the predisposition of organs and systems to ADR is observed remarkably in the hepatobiliary and gastrointestinal systems at 41.8% vs. 36.2%, p < 0.0001, and the classes of drugs implicated in the ADRs are lopinavir-ritonavir 16.3%, antibiotics 24.1%, and hydroxychloroquine12.8%. Furthermore, the duration of hospitalization and polypharmacy are significantly higher in patients with ADRs at 14.13 ± 7.87 versus 9.55 ± 7.90, p < 0.001, and 9.74 ± 5.51 versus 6.98 ± 4.36, p < 0.0001, respectively. Comorbidities are detected in 42.5% of patients and 75.2%, of patients with DM, and HTN, displaying significant ADRs, p-value < 0.05. This is a symbolic study providing a comprehensive acquaintance of the importance of APIs in detecting hospitalized ADRs, revealing increased detection rates and robust assertive values with insignificant costs, incorporating the hospital EMR database, and enhancing transparency and time effectiveness.

Local Delivery of Azithromycin Nanoformulation Attenuated Acute Lung Injury in Mice.

Humanity has suffered from the coronavirus disease 2019 (COVID-19) pandemic over the past two years, which has left behind millions of deaths. Azithromycin (AZ), an antibiotic used for the treatment of several bacterial infections, has shown antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as against the dengue, Zika, Ebola, and influenza viruses. Additionally, AZ has shown beneficial effects in non-infective diseases such as cystic fibrosis and bronchiectasis. However, the systemic use of AZ in several diseases showed low efficacy and potential cardiac toxicity. The application of nanotechnology to formulate a lung delivery system of AZ could prove to be one of the solutions to overcome these drawbacks. Therefore, we aimed to evaluate the attenuation of acute lung injury in mice via the local delivery of an AZ nanoformulation. The hot emulsification-ultrasonication method was used to prepare nanostructured lipid carrier of AZ (AZ-NLC) pulmonary delivery systems. The developed formulation was evaluated and characterized in vitro and in vivo. The efficacy of the prepared formulation was tested in the bleomycin (BLM) -mice model for acute lung injury. AZ-NLC was given by the intratracheal (IT) route for 6 days at a dose of about one-eighth oral dose of AZ suspension. Samples of lung tissues were taken at the end of the experiment for immunological and histological assessments. AZ-NLC showed an average particle size of 453 nm, polydispersity index of 0.228 ± 0.07, zeta potential of -30 ± 0.21 mV, and a sustained release pattern after the initial 50% drug release within the first 2 h. BLM successfully induced a marked increase in pro-inflammatory markers and also induced histological changes in pulmonary tissues. All these alterations were significantly reversed by the concomitant administration of AZ-NLC (IT). Pulmonary delivery of AZ-NLC offered delivery of the drug locally to lung tissues. Its attenuation of lung tissue inflammation and histological injury induced by bleomycin was likely through the downregulation of the p53 gene and the modulation of Bcl-2 expression. This novel strategy could eventually improve the effectiveness and diminish the adverse drug reactions of AZ. Lung delivery could be a promising treatment for acute lung injury regardless of its cause. However, further work is needed to explore the stability of the formulation, its pharmacokinetics, and its safety.

Pharmacoinformatic study of inhibitory potentials of selected flavonoids against papain-like protease and 3-chymotrypsin-like protease of SARS-CoV-2

Background: Inhibition of papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is projected to terminate its replication. Hence, these proteases represent viable therapeutic targets. Methods: Sixty-one flavonoids with reported activities against other RNA viruses were selected and docked in PLpro and 3CLpro. Flavonoids with better binding energies compared to reference inhibitors (lopinavir and ritonavir) in their interaction with PLpro and 3CLpro were selected for drug-likeness and ADMET analysis. The best representative flavonoid for each protease from the ADMET filtering analysis was subjected to molecular dynamics simulations (MDS) and clustering analysis of the trajectory files. Results: Licorice, ugonin M, procyanidin, silymarin, and gallocatechin gallate had better binding energies (-11.8, -10.1, -9.8, -9.7 and -9.6 kcal/mol respectively) with PLpro compared to lopinavir and ritonavir (-9.1 and -8.5 kcal/mol respectively). Also, isonymphaeol B, baicalin, abyssinone II, tomentin A, and apigetrin had better binding energies (-8.7, -8.3, -8.2, -8.1, and -8.1 kcal/mol respectively) with 3CLpro compared to lopinavir and ritonavir (-7.3 and -7.1 kcal/mol respectively). These flavonoids interacted with the proteases via hydrogen and non-hydrogen bonding. Of these flavonoids, silymarin and isonymphaeol B demonstrated most favourable combination of attributes in terms of binding energies, compliance with Lipinski rule for drug-likeness and favourable pharmacokinetics in silico. These two flavonoids exhibited appreciable degree of structural stability, maintaining strong interaction with residues in the different representative clusters selected during the MDS run. Conclusion: Silymarin and isonymphaeol B are proposed for further studies as compounds with potential activities against SARS-CoV-2. Supplementary Information: The online version contains supplementary material available at 10.1186/s40816-022-00347-y.

SARS-CoV-2 Delta Variant is Recognized Through GRP78 Host-Cell Surface Receptor, In Silico Perspective.

Different SARS-CoV-2 new variants emerged and spread during the past few months, sparking infections and death counts. The new variant B.1.617 (delta variant) sparked in India in the past few months, causing the highest records. The B.1.617 variant of SARS-CoV-2 has the double mutations E484Q and L452R on its spike Receptor Binding Domain (RBD). The first mutation is like the reported South African and the Brazilian variants (501.V2 and B.1.1.248). This mutation lies in the region C480-C488, which we predicted before to be recognized by the host-cell receptor; Glucose Regulated Protein 78 (GRP78). In the current study, we test the binding affinity of the host-cell receptor GRP78 to the delta variant spike RBD using molecular docking and molecular dynamics simulations of up to 100 ns. Additionally, the ACE2-RBD is tested by protein-protein docking. The results reveal equal average binding affinities of the GRP78 against wildtype and delta variant spikes. This supports our previous predictions of the contribution of GRP78 in SARS-CoV-2 spike recognition as an auxiliary route for entry.

Targeting SARS-CoV-2 endoribonuclease: a structure-based virtual screening supported by in vitro analysis.

Researchers are focused on discovering compounds that can interfere with the COVID-19 life cycle. One of the important non-structural proteins is endoribonuclease since it is responsible for processing viral RNA to evade detection of the host defense system. This work investigates a hierarchical structure-based virtual screening approach targeting NSP15. Different filtering approaches to predict the interactions of the compounds have been included in this study. Using a deep learning technique, we screened 823,821 compounds from five different databases (ZINC15, NCI, Drug Bank, Maybridge, and NCI Diversity set III). Subsequently, two docking protocols (extra precision and induced fit) were used to assess the binding affinity of the compounds, followed by molecular dynamic simulation supported by the MM-GBSA free binding energy. Interestingly, one compound (ZINC000104379474) from the ZINC15 database has been found to have a good binding affinity of - 7.68 kcal/Mol. The VERO-E6 cell line was used to investigate its therapeutic effect in vitro. Half-maximal cytotoxic concentration and Inhibitory concentration 50 were determined to be 0.9 mg/ml and 0.01 mg/ml, respectively; therefore, the selectivity index is 90. In conclusion, ZINC000104379474 was shown to be a good hit for targeting the virus that needs further investigations in vivo to be a drug candidate.

Pulmonary Delivery of Hydroxychloroquine Nanostructured Lipid Carrier as a Potential Treatment of COVID-19.

Coronavirus Disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2. Pneumonia is considered the most severe and long-term complication of COVID-19. Among other drugs, hydroxychloroquine (HCQ) was repurposed for the management of COVID-19; however, low efficacy and cardiac toxicity of the conventional dosage form limited its use in COVID-19. Therefore, utilizing nanotechnology, a pulmonary delivery system of HCQ was investigated to overcome these limitations. HCQ was formulated in nanostructured lipid carriers (HCQ-NLCs) using the hot emulsification-ultrasonication method. Furthermore, the prepared formulation was evaluated in vitro. Moreover, the efficacy was tested in vivo in a bleomycin-induced acute lung injury mice model. Intriguingly, nanoformulations were given by the intratracheal route for 6 days. HCQ-NLCs showed a mean particle size of 277 nm and a good drug release profile. Remarkably, acute lung injury induced by bleomycin was associated with a marked elevation of inflammatory markers and histological alterations in lung tissues. Astoundingly, all these changes were significantly attenuated with HCQ-NLCs. The pulmonary delivery of HCQ-NLCs likely provided adequate targeting to lung tissues. Nevertheless, there is hope that this novel strategy will eventually lead to the improved effectiveness and diminished probability of alarming adverse drug reactions.

Interference of Chaga mushroom terpenoids with the attachment of SARS-CoV-2; in silico perspective.

Finding a potent inhibitor to the pandemic SARS-CoV-2 is indispensable nowadays. Currently, in-silico methods work as expeditious investigators to screen drugs for possible repurposing or design new ones. Targeting one of the possible SARS-CoV-2 attachment and entry receptors, Glucose-regulated protein 78 (GRP78), is an approach of major interest. Recently, GRP78 was reported as a recognized representative in recognition of the latest variants of SARS-CoV-2. In this work, molecular docking and molecular dynamics simulations were performed on the host cell receptor GRP78. With its many terpenoid compounds, Chaga mushroom was tested as a potential therapeutic against the SARS-CoV-2 receptor, GRP78. Results revealed low binding energies (high affinities) toward the GRP78 substrate-binding domain ß (SBDß) of Chaga mushroom terpenoids. Even the highly specific cyclic peptide Pep42, which selectively targeted GRP78 over cancer cells in vivo, showed lower binding affinity against GRP78 SBDß compared to the binding affinities of terpenoids. These are auspicious results that need to be tested experimentally. Intriguingly, terpenoids work as a double sword as they can be used to interfere with VUI 202,012/01, 501.V2, and B.1.1.248 variants of SARS-CoV-2 spike recognition.

Multidimensional in silico strategy for identification of natural polyphenols-based SARS-CoV-2 main protease (Mpro) inhibitors to unveil a hope against COVID-19.

SARS-CoV-2, a rapidly spreading new strain of human coronavirus, has affected almost all the countries around the world. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. Thus, there is an urgent need to boost up research for the development of effective therapeutics against COVID-19. In the current study, we investigated the efficacy of 81 medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro by using various in silico techniques. The interaction affinities of polyphenolic compounds towards SARS-CoV-2 Mpro was assessed via intramolecular (by Quantum Mechanic), intermolecular (by Molecular Docking), and spatial (by Molecular Dynamic) simulations. Our obtained result demonstrate that Hesperidin, rutin, diosmin, and apiin are most effective compounds agents against SARS-CoV-2 Mpro as compared to Nelfinavir (positive control). This study will hopefully pave a way for advanced experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

Molecular dynamics simulations and MM-GBSA reveal novel guanosine derivatives against SARS-CoV-2 RNA dependent RNA polymerase.

According to the World Health Organization (WHO), SARS-CoV-2 is responsible for more than 5 M deaths and is reported in 223 countries infecting 250+ M people. Despite the current vaccination momentum, thousands of people die every day by COVID-19. Suggesting possible blockers of the viral RNA-dependent RNA polymerase is highly needed for potential effective therapeutics against SARS-CoV-2. This study utilizes combined molecular dynamics simulation and molecular docking to test novel guanosine derivatives against SARS-CoV-2 RdRp. Results reveal the binding potency of nineteen guanosine derivatives against SARS-CoV-2 solved structures. The bulky moieties (hydroxyl or fluorated phenyl moieties) added to the 2' position of the ribose ring positively impacted the binding affinity to RdRp. The current in silico study represents a one-step-ahead for suggesting new possible blockers of SARS-CoV-2 RdRp that are yet to be verified in the wet lab. It offers new potential binders or blockers of RdRp that bind to the protein active site tighter than remdesivir. The latter was approved by the food and drug administration (FDA) for emergency use against COVID-19 last year.

A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses.

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.

Dietary stigmastane-type saponins as promising dual-target directed inhibitors of SARS-CoV-2 proteases: a structure-based screening.

Despite the development of COVID-19 vaccines, at present, there is still no approved antiviral drug against the pandemic. The SARS-CoV-2 3-chymotrypsin-like proteases (S-3CLpro) and papain-like protease (S-PLpro) are essential for the viral proliferation cycle, hence attractive drug targets. Plant-based dietary components that have been extensively reported for antiviral activities may serve as cheap sources of preventive nutraceuticals and/or antiviral drugs. A custom-made library of 176 phytochemicals from five West African antiviral culinary herbs was screened for potential dual-target-directed inhibitors of S-3CLpro and S-PLpro in silico. The docking analysis revealed fifteen steroidal saponins (FSS) from Vernonia amygdalina with the highest binding tendency for the active sites of S-3CLpro and S-PLpro. In an optimized docking analysis, the FSS were further docked against four equilibrated conformers of the S-3CLpro and S-PLpro. Three stigmastane-type steroidal saponins (vernonioside A2, vernonioside A4 and vernonioside D2) were revealed as the lead compounds. These compounds interacted with the catalytic residues of both S-3CLpro and S-PLpro, thereby exhibiting dual inhibitory potential against these SARS-CoV-2 cysteine proteases. The binding free energy calculations further corroborated the static and optimized docking analysis. The complexed proteases with these promising phytochemicals were stable during a full atomistic MD simulation while the phytochemicals exhibited favourable physicochemical and ADMET properties, hence, recommended as promising inhibitors of SARS-CoV-2 cysteine proteases.

Scoping insight on antiviral drugs against COVID-19.

BACKGROUND: COVID-19 is an ongoing viral pandemic produced by SARS-CoV-2. In light of in vitro efficacy, several medications were repurposed for its management. During clinical use, many of these medications produced inconsistent results or had varying limitations. OBJECTIVE: The purpose of this literature review is to explain the variable efficacy or limitations of Lopinavir/Ritonavir, Remdesivir, Hydroxychloroquine, and Favipiravir in clinical settings. METHOD: A study of the literature on the pharmacodynamics (PD), pharmacokinetics (PK), safety profile, and clinical trials through academic databases using relevant search terms. RESULTS & DISCUSSION: The efficacy of an antiviral drug against COVID-19 is associated with its ability to achieve therapeutic concentration in the lung and intestinal tissues. This efficacy depends on the PK properties, particularly protein binding, volume of distribution, and half-life. The PK and PD of the model drugs need to be integrated to predict their limitations. CONCLUSION: Current antiviral drugs have varying pharmacological constraints that may associate with limited efficacy, especially in severe COVID-19 patients, or safety concerns.

SARS-CoV-2 host cell entry: an in silico investigation of potential inhibitory roles of terpenoids.

BACKGROUND: Targeting viral cell entry proteins is an emerging therapeutic strategy for inhibiting the first stage of SARS-CoV-2 infection. In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 (hACE2), human transmembrane protease serine 2 (TMPRSS2), and the spike (S) proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV. In silico absorption-distribution-metabolism-excretion-toxicity (ADMET) and drug-likeness prediction, molecular dynamics (MD) simulation, binding free energy calculations, and clustering analysis of MD simulation trajectories were performed on the top docked terpenoids to respective protein targets. RESULTS: The results revealed eight terpenoids with high binding tendencies to the catalytic residues of different targets. Two pentacyclic terpenoids (24-methylene cycloartenol and isoiguesteri) interacted with the hACE2 binding hotspots for the SARS-CoV-2 spike protein, while the abietane diterpenes were found accommodated within the S1-specificity pocket, interacting strongly with the active site residues TMPRSS2. 3-benzoylhosloppone and cucurbitacin interacted with the RBD and S2 subunit of SARS-CoV-2 spike protein respectively. These interactions were preserved in a simulated dynamic environment, thereby, demonstrating high structural stability. The MM-GBSA binding free energy calculations corroborated the docking interactions. The top docked terpenoids showed favorable drug-likeness and ADMET properties over a wide range of molecular descriptors. CONCLUSION: The identified terpenoids from this study provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell-mediated entry proteins. They are therefore recommended for further in vitro and in vivo studies towards developing entry inhibitors against the ongoing COVID-19 pandemic.

Structure-based virtual screening suggests inhibitors of 3-Chymotrypsin-Like Protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum.

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CLpro from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CLpro in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CLpro. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys145 and His41), the oxyanion loop (residues 138-145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.

Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.

BACKGROUND: SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. METHODS: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. RESULTS: The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (- 8.13 ± 0.45 kcal/mol, - 8.09 ± 0.67 kcal/mol, - 8.09 ± 0.64 kcal/mol, and - 8.07 ± 0.73 kcal/mol, respectively). CONCLUSIONS: The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally.

Recognition through GRP78 is enhanced in the UK, South African, and Brazilian variants of SARS-CoV-2; An in silico perspective.

New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell.

COVID-19 and Cell Stress.

The present century will undoubtedly be marked with the COVID-19 global health crisis. It is not time yet to talk about the total number of deaths and hospitalizations, as they are enormously growing daily. Understanding the nature of COVID-19-induced pneumonia is vital in order to deal with the associated health complications. Cell stress is an established mechanism known to be associated with infection and cancer. Different proteins crucial for cellular response to stress are reported to be a possible target to stop the infection and to reduce the chemo-resistance in cancer. Heat shock protein (HSP) families of chaperones play an essential role in cells both in normal state and under stress. The upregulation of HSP5A, also termed GRP78 or Bip, is reported in different viral infections. This chapter introduces the current knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the COVID-19 pandemic, and cell stress aimed at defining possible strategies to combat the COVID-19 pandemic.