An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloprotein-ase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients

Background: The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. Objective(s): This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. Method(s): This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. Result(s): The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Conclusion(s): Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predict-ing lung involvement in COVID-19 and directing clinical outcomes.Copyright © 2023 Demir NA et al. Licensee African Health Sciences.

Ultradiluted SARS-CoV-2 Spike Protein mitigates hyperinflammation in lung via ferritin and MMP-9 regulation in BALB/c mice.

AIM: This study investigated the prophylactic and therapeutic role of ultradiluted preparation of the Delta variant of SARS-CoV-2 recombinant spike (S) protein during S antigen-induced inflammatory process of disease progression along with the probable mechanism of action. MAIN METHODS: Ultradiluted S protein (UDSP) was prepared and administered orally to adult BALB/c mice before and after administration of S antigen intranasally. After an observation period of 72 h, animals were sacrificed and expression level of ferritin was assayed through ELISA. The genetic expressions of cytokines, IL-6, IL-10, IL-1ß, TNFα, IL-17, MMP-9, TIMP-1, ferritin light and heavy chains, and mitochondrial ferritin from lung tissues were investigated through RT-PCR. Formalin-fixed lung tissue sections were stained with hematoxylin and eosin to observe the degree of pathological changes. The activity of MMP-9 in lung tissues was investigated through gelatin zymography and immunofluorescence of MMP-9 in lung tissue sections was performed to revalidate the finding from gelatin zymography. Systems biology approach was used to elucidate a probable pathway where UDSP attenuated the inflammation through the regulation of pro- and anti-inflammatory cytokines. KEY FINDINGS: UDSP attenuated the S antigen-induced hyperinflammation in the lung by regulating pro- and anti-inflammatory cytokines, calming cytokine storm, reducing ferritin level both in transcriptional and translational levels, and restoring critical ratio of MMP-9: TIMP-1. SIGNIFICANCE: Our findings suggest a probable pathway by which UDSP might have attenuated inflammation through the regulation of cytokines, receptors, and other molecules. This proclaims UDSP as a promising antiviral agent in the treatment of COVID-19-induced immunopathogenesis.

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality.

BACKGROUND AND METHODS: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. RESULTS: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. CONCLUSIONS: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men.

Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 with SARS CoV-2 infections

SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2. Matrix metalloproteinases-9 (MMP-9) performs a crucial physiological role. In addition to its roleICLEin the molecular basis of lung fibrosis, this enzyme may also play a part in the "cytokine storm," which may represent one of the potential scenarios during coronavirus infection. Tissue inhibitors of metalloproteinase (TIMPs) are well-known for their ability to regulate MMP activity during remodeling of the extracellular matrix. As cytokines, they are also thought of as signaling molecules that impact on a wide range of biological processes. This study aimed to investigate the link between each of MMP-9 and TIMP-1, and COVID19 disease. A total of 58 COVID-19 patients and 30 apparently healthy adults enrolled in this study. The ORF1ab, E and N genes of SARS-CoV-2 were detected using multiplex real-time PCR, while the ELISA technique was used to estimate the level of serum MMP-9, TIMP-1, and C-reactive protein (CRP). The study results demonstrated higher concentrations of MMP-9 in COVID-19 patients (2810 ± 1160 pg/ml) compared to controls (2110 ± 850 pg/ml), with non-significant differences (p=0.002). Unlike, TIMP-1, showed considerably higher levels in the patient's group (541.53 ± 201.42 pg/ml) than in controls (276.33 ± 67.26 pg/ml) with high significant differences (p ≤ 0.001). Considering this study, TIMP-1 in COVID patients most likely play an important role in inflammatory response. Its clinical utility as a biomarker may be insufficient, but it provides a useful data in the diagnosis of COVID‐19. © 2023, Bangladesh Society for Microbiology, Immunology and Advanced Biotechnology. All rights reserved.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes.

COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

Association of Candida Species with Novel SARS-CoV-2 and Biomarkers for Fungal Premalignant Oral Lesions.

Oral fungal infections can be caused by certain species of fungi among which candida albicans is the most implicated. Oral candidiasis is correlated with multiple conditions, such as coronavirus disease-2019, oral leukoplakia and oral erythroplakia. Tenascin is a glycoprotein and is present at the site of tissue injury and chronic inflammation, and tends to be over-expressed in cases of malignancy. Matrix metalloproteinase-9 belongs to a family of zinc-dependent endopeptidases and is involved in the degradation of extracellular matrix, leading to tissue invasion and metastasis. The current narrative review was planned to shed light on the fungal co-infections of coronavirus disease-2019 and molecular mechanisms of matrix metalloproteinase-9 and tenascin involved in the pathogenesis of fungus-associated oral leukoplakia and oral erythroplakia.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Impact of High Serum Levels of MMP-7, MMP-9, TGF-ß and PDGF Macrophage Activation Markers on Severity of COVID-19 in Obese-Diabetic Patients.

OBJECTIVE: The aim of this study was to identify an association between the severity of COVID-19 in obese-diabetic patients and altered serum levels of MMP-7, MMP-9, TGF-ß, and PDGF macrophage activation markers. METHODOLOGY: The study included 70 COVID-19 patients, divided into two groups: Group 1 included: Obese COVID-19 patients with type 2 diabetes mellitus (T2D, n=22 patients) and group 2 included; non-obese, non-diabetic COVID-19 patients as an age- and sex-matched control group (n=48 patients). Serum levels of the tested biomarkers were measured by ELISA at admission and after one weak follow-up. RESULTS: There was a significant reduction in the serum levels of LBP in obese-diabetic COVID-19 patients versus the control group (8.34±3.94 vs 20.78±7.61) (p 0.0001). Significant elevation of MMP-7, MMP-9, PDGF and TGF-ß was detected in obese diabetic COVID-19 patients compared to the non-obese non-diabetic group: 1044.7±519.6 vs 405.6±164.1, 483.05±46.5 vs 173.31±76.26, 154.5±62.78 vs 39.77±21.52, and 603.05±258.82 vs 180.29±97.17, respectively. The serum levels of macrophage activation markers in obese-diabetic patients one week after admission revealed that patients with acute respiratory distress syndrome (ARDS) had significantly higher serum levels of MMP-7 and MMP-9 than non-ARDS patients (p 0.02 and p 0.01 respectively). CONCLUSION: Macrophages were mainly polarized towards the M2 phenotype in obese-diabetic COVID-19 patients with significant upregulation of the pro-fibrotic markers MMP-7, MMP-9, PDGF, and TGF-ß. Thus, high levels of MMP-7 and MMP-9 are associated with ARDS in severe COVID-19 disease among obese-diabetic patients.

Intricate relationship between SARS-CoV-2-induced shedding and cytokine storm generation: A signaling inflammatory pathway augmenting COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its ability to induce cytokine release syndrome, can set up a generalized inflammatory response together with activating multiple inflammatory pathways, which contributes to a dramatic increase in the number of mortalities and morbidities worldwide. Reportedly, the manipulative nature of coronavirus disease 2019 (COVID-19), which targets the immune system, often focuses on specific inflammation-related pathways, usually confined to interleukins and tumor necrosis factor-α (TNF-α), with a great emphasis on therapeutic approaches targeting the inhibition of these inflammatory mediators. The involvement of a disintegrin and metalloprotease 17 (ADAM-17) and matrix metalloproteinase-9 (MMP-9) in the pathogenesis of COVID-19, through their ability to potentiate the cytokine storm during an episode of SARS-CoV-2 infection, often goes unnoticed. In this review, the intricate relationship between ADAM-17 and MMP-9 together with angiotensin-converting enzyme 2 (ACE-2) as the main target for SARS-CoV-2 is highlighted in detail through a compilation of evidence-based literature; thus, we shed light on a proposed inflammatory pathway that COVID-19 may exploit to provoke an inflammatory response of a complex nature. Conclusively, our proposed mechanism acts as a means to developing a therapeutic approach aimed at modulating the intricate communication between ADAM-17 and MMP-9, where a great emphasis on the role of ACE-2 shedding and subsequent elevation in angiotensin II (Ang-II) levels is crucial to understanding the awry inflammatory response in patients with COVID-19. From this concept, designing a therapeutic strategy targeting multiple inflammatory mediators and enzymes simultaneously is another approach to unravel this global pandemic.

Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine.

Over the last two decades, a large number of non-communicable/chronic disorders reached an epidemic level on a global scale such as diabetes mellitus type 2, cardio-vascular disease, several types of malignancies, neurological and eye pathologies-all exerted system's enormous socio-economic burden to primary, secondary, and tertiary healthcare. The paradigm change from reactive to predictive, preventive, and personalized medicine (3PM/PPPM) has been declared as an essential transformation of the overall healthcare approach to benefit the patient and society at large. To this end, specific biomarker panels are instrumental for a cost-effective predictive approach of individualized prevention and treatments tailored to the person. The source of biomarkers is crucial for specificity and reliability of diagnostic tests and treatment targets. Furthermore, any diagnostic approach preferentially should be noninvasive to increase availability of the biomaterial, and to decrease risks of potential complications as well as concomitant costs. These requirements are clearly fulfilled by tear fluid, which represents a precious source of biomarker panels. The well-justified principle of a "sick eye in a sick body" makes comprehensive tear fluid biomarker profiling highly relevant not only for diagnostics of eye pathologies but also for prediction, prognosis, and treatment monitoring of systemic diseases. One prominent example is the Sicca syndrome linked to a cascade of severe complications that include dry eye, neurologic, and oncologic diseases. In this review, protein profiles in tear fluid are highlighted and corresponding biomarkers are exemplified for several relevant pathologies, including dry eye disease, diabetic retinopathy, cancers, and neurological disorders. Corresponding analytical approaches such as sample pre-processing, differential proteomics, electrophoretic techniques, high-performance liquid chromatography (HPLC), enzyme-linked immuno-sorbent assay (ELISA), microarrays, and mass spectrometry (MS) methodology are detailed. Consequently, we proposed the overall strategies based on the tear fluid biomarkers application for 3P medicine practice. In the context of 3P medicine, tear fluid analytical pathways are considered to predict disease development, to target preventive measures, and to create treatment algorithms tailored to individual patient profiles.

MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p < 0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p < 0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p < 0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels. Age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.

SARS-CoV-2: is there neuroinvasion?

BACKGROUND: SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. MAIN BODY: We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. CONCLUSIONS: While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.

Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.

Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity.

Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis.

AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.