Porphyrins with combinations of 4-carboxyphenyl and 4-hydroxyphenyl substituents in meso-positions as anti-HIV-1 agents.

A series of 4-carboxyphenyl/4-hydroxyphenyl meso-substituted porphyrins were synthesized, purified, and characterized. The compounds exhibited anti-HIV-1 activities, in vitro, under both non-photodynamic (non-PDT) and photodynamic (PDT) conditions. Specifically, the porphyrins inhibited HIV-1 virus entry, with c-PB2(OH)2 and PB(OH)3 showing significant anti-HIV-1 activity. All of the porphyrins inhibited HIV-1 subtype B and C virus entry under PDT conditions. Our study demonstrated that the compounds bearing combinations of 4-carboxyphenyl/4-hydroxyphenyl moieties were not toxic even at higher concentrations, as compared to the reference porphyrins 5,10,15,20-tetra-(4-carboxyphenyl)porphyrin (TCPP) and 5,10,15,20-tetra-(4-hydroxyphenyl)porphyrin (THPP), under PDT conditions. This study underscores the promising potential of these compounds as HIV entry inhibitors in both non-PDT and PDT scenarios.

Construction of a HIV-1 subtype C 3D model using homology modeling and in-silico docking, molecular dynamics simulation, and MM-GBSA calculation of second-generation HIV-1 maturation inhibitor(s).

Maturation inhibitors (MIs) efficiently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1) leading to the production of immature and non-infectious virus particles. We have previously reported that second-generation MIs were more potent than bevirimat (BVM) against HIV-1 subtype C. In-silico studies on interaction of with BVM and their analogs have been limited to HIV-1 subtype B(5I4T) due to lack of an available 3D structure for HIV-1 subtype C virus. In our current study, we have developed a 3D model of HIV-1C Gag CA-SP1 region using protein homology modeling with HIV-1 subtype B(514T) as a template. The HIV-1 C homology model generated was extensively validated using several online tools and served as a template to perform molecular docking studies with eight well-characterized MIs. The docked complex of HIV-1C and all nine MIs was subjected to molecular dynamics simulation for 100 ns using AMBER and binding free energy calculations were done using MM-GBSA. Based on our data, CV8611 exhibited highest binding energy of -6.5 Kcal/mol among all BVM analogs. CV8611 formed strong interactions with Gly222 and Met235 of HIV-1C Gag CA-SP1 during MD simulation and remained intact. The root mean square deviation and root mean square fluctuation values of the complex were stable during the simulations. Our study is the first to report construction and validation of 3D model for the HIV-1C Gag CA-SP1, which could serve as a crucial tool in the structure-aided design of novel and broadly acting maturation inhibitors.Communicated by Ramaswamy H. Sarma.

Edelfosine reactivates latent HIV-1 reservoirs in myeloid cells through activation of NF-κB and AP1 pathway.

The persistence of latent HIV-1 reservoirs in cells presents a formidable challenge towards a complete HIV cure. Edelfosine is an FDA-approved investigational, anti-neoplastic drug. In this study, we aimed to investigate its role as a HIV-1 Latency Reversal Agent (LRA) using latency model cell lines. Our findings demonstrated that edelfosine reactivated latent HIV-1 viruses in myeloid cells in a dose and time-dependent manner. The mechanism of reactivation by edelfosine involved the activation of NF-κB and AP1 pathways in these cells. The reactivated virus was non-infectious. Delineating the mechanism of non-infectious virus production revealed an increased stabilization of cellular APOBEC3G protein as well as its enhanced incorporation into the released viruses. Thus, our study demonstrated for the first time an additional role of edelfosine in reactivation of latent HIV-1 and production of non-infectious virus. Our results have paved the way for repurposing of edelfosine as a novel HIV-1 latency reversal agent.

Construction and characterization of a full-length, replication-competent and infectious enhanced green fluorescence protein-tagged HIV-1 subtype C molecular clone.

HIV-1 subtype C virus accounts for nearly 50% of the total HIV infections globally. Despite this high prevalence, our understanding of subtype C specific infections remains limited due to lack of an in vitro model system. This is the first report of construction and characterization of a full-length and infectious EGFP-tagged HIV-1 subtype C molecular clone. The EGFP gene was inserted in-frame between the Nef and Env sequence in the HIV genome. The recombinant virus displayed expression of viral genes, infectivity and replication kinetics similar to the parental virus. VSV-G pseudotyping of the recombinant virus led to enhancement of HIV infection. The presence of the EGFP gene provides a rapid, easy and quantitative measure of HIV infection by flow cytometry and fluorescence microscopy. This clone will serve as an extremely beneficial tool to study HIV-1 subtype C specific infections.

Two cationic meso-thiophenium porphyrins and their zinc-complexes as anti-HIV-1 and antibacterial agents under non-photodynamic therapy (PDT) conditions.

The anti-HIV-1 and antimicrobial activities of novel cationic meso-thiophenium porphyrins and their zinc-complex are reported under in vitro non-photodynamic (PDT) conditions. While all the cationic porphyrins led to the inhibition of de novo virus infection, the Zn(II)-complexes of T2(OH)2M (A2B2-type) and T(OH)3M (AB3-type) displayed potent inhibition of HIV-1 entry with T2(OH)2MZn displaying maximal anti-HIV activity. The Zinc complex of both the thiophenium porphyrins T2(OH)2M and T(OH)3M also depicted antibacterial activities against Escherichia coli (ATCC 25922) and more prominently against Staphylococcus aureus (ATCC 25923). Again, the antibacterial activity was more potent for T2(OH)2MZn. Our study highlighted that the presence of two thiophenium groups at the meso-positions of the A2B2-type porphyrins along with zinc strongly enhanced anti-HIV and antimicrobial properties of these novel thiophenium porphyrins under non-PDT conditions.

Buccal swabs as non-invasive specimens for detection of severe acute respiratory syndrome coronavirus-2.

INTRODUCTION: The current gold standard for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA involves subjecting nasopharyngeal or oropharyngeal swabs to reverse transcription quantitative PCR (RT-qPCR). However, both sample types need to be collected by trained professionals. Using self-collected buccal swabs as an alternative could simplify and accelerate diagnosis of coronavirus disease 2019 (COVID-19). OBJECTIVE: To assess self-collected buccal swab samples as an alternative method for SARS-CoV-2 detection in patients with COVID-19. METHODS: Buccal swab samples were self-collected by 73 patients with COVID-19. Total RNA was extracted using Qiagen kits. RNA encoding the SARS-CoV-2 Env protein and human RNase P as an internal control was amplified using the TRUPCR® SARS-CoV-2 RT-qPCR kit version 2.1 and a Bio-Rad CFX96 Real-Time Detection System. RESULT: The sensitivity of RT-qPCR from buccal swabs was 58.9% (43/73; 95% confidence interval [CI] 46.77%-70.27%) and that of RT-qPCR from saliva was 62.90% (39/62; 95% CI 49.69%-74.84%) taking positive SARS-CoV-2 RT-qPCR from nasopharyngeal swabs as the gold standard. CONCLUSION: Self-collected buccal swabs are promising alternatives to nasopharyngeal or oropharyngeal swabs for SARS CoV-2 detection.

A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors.

BACKGROUND: Maturation inhibitors (MIs) potently block HIV-1 maturation by inhibiting the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a highly efficacious first-in-class MI against HIV-1 subtype B isolates, elicited sub-optimal efficacy in clinical trials due to polymorphisms in the CA-SP1 region of the Gag protein (SP1:V7A). HIV-1 subtype C inherently contains this polymorphism thus conferring BVM resistance, however it displayed sensitivity to second generation BVM analogs. RESULTS: In this study, we have assessed the efficacy of three novel second-generation MIs (BVM analogs: CV-8611, CV-8612, CV-8613) against HIV-1 subtype B and C isolates. The BVM analogs were potent inhibitors of both HIV-1 subtype B (NL4-3) and subtype C (K3016) viruses. Serial passaging of the subtype C, K3016 virus strain in the presence of BVM analogs led to identification of two mutant viruses-Gag SP1:A1V and CA:I201V. While the SP1:A1V mutant was resistant to the MIs, the CA:I120V mutant displayed partial resistance and a MI-dependent phenotype. Further analysis of the activity of the BVM analogs against two additional HIV-1 subtype C strains, IndieC1 and ZM247 revealed that they had reduced sensitivity as compared to K3016. Sequence analysis of the three viruses identified two polymorphisms at SP1 residues 9 and 10 (K3016: N9, G10; IndieC1/ZM247: S9, T10). The N9S and S9N mutants had no change in MI-sensitivity. On the other hand, replacing glycine at residue 10 with threonine in K3016 reduced its MI sensitivity whereas introducing glycine at SP1 10 in place of threonine in IndieC1 and ZM247 significantly enhanced their MI sensitivity. Thus, the specific glycine residue 10 of SP1 in the HIV-1 subtype C viruses determined sensitivity towards BVM analogs. CONCLUSIONS: We have identified an association of a specific glycine at position 10 of Gag-SP1 with an MI susceptible phenotype of HIV-1 subtype C viruses. Our findings have highlighted that HIV-1 subtype C viruses, which were inherently resistant to BVM, may also be similarly predisposed to exhibit a significant degree of resistance to second-generation BVM analogs. Our work has strongly suggested that genetic differences between HIV-1 subtypes may produce variable MI sensitivity that needs to be considered in the development of novel, potent, broadly-active MIs.

miR-150-mediated increase in glucose uptake in HIV-infected cells.

Replication of HIV-1 inside host cells is dependent on both viral and host factors. MicroRNAs are small noncoding RNAs that regulate protein synthesis. MicroRNAs may control viral replication either by directly targeting the viral genome or indirectly through cellular proteins that are required during the viral lifecycle. HIV infection may, in turn, regulate host microRNA expression to facilitate its propagation inside cells. miR-150 has been reported to be an essential factor involved in T-cell activation and may serve as a biomarker for HIV disease progression. The current study provides valuable insights into the role of miR-150 in HIV infection. We quantified miR-150 expression in HIV-infected Jurkat cells and observed a time-dependent increase in the expression of miR-150. In addition, HIV infection led to an enhanced influx of glucose inside the infected cells, which further increased on overexpression of miR-150. The increased uptake of glucose was due to miR-150-mediated increase in expression of glucose transporter-1 (GLUT1). In an attempt to decipher the mechanism, we identified that HIV Tat protein enhanced the expression of miR-150 which then upregulated GLUT1 in HIV-infected cells. In summary, this study sheds light on the role of miR-150 in HIV infection and paves the way for miR-150 as a novel therapeutic target against HIV-1.

Identification of MHC Class I bound peptides of Francisella tularensis Live Vaccine Strain using mass spectrometry.

Tularemia, a zoonosis generally prevalent in the northern half of the globe, is caused by Francisella tularensis. Among various Francisella tularensis species, subspecies tularensis is the most pathogenic to humans causing the infection through an airborne route, abrasions in the skin, and contact with infected animals. At present no approved vaccine exists for this intracellular pathogen. Principal defensive immunity against Francisella is T-cell mediated immunity, hence, picking out significant T-cell antigens is obligatory for Francisella vaccine advancement. In the present study, an immunoproteomics approach was employed to discover T-cell antigens by infecting dendritic cells derived from monocytes with F. tularensis NCTC10857, followed by immunoaffinity isolation of MHC class I molecules and acidic elution of bound peptides. The tandem mass spectrometry technique was used to identify the sequences of the isolated peptides. Ten MHC class I restricting Francisella derived peptides were successfully identified. Top three isolated peptide sequences were modeled and used for in silico docking study to substantiate their interaction and characterize their binding potential. Virtual docking studies further confirmed a high binding affinity for top three peptides with MHC class I molecule. The outcome of this study has led to identification of the probable vaccine candidates for human studies based on T cell-antigens against Francisella.

Dual activity of amphiphilic Zn(II) nitroporphyrin derivatives as HIV-1 entry inhibitors and in cancer photodynamic therapy.

Two Zn(II) nitro porphyrin derivatives bearing combinations of meso-4-nitrophenyl and meso-4-methylpyridinium moieties and their free-base precursors were synthesized through one-pot microwave process, purified and characterized. The biological activity of these nitroporphyrins was assessed under both photodynamic and non-photodynamic conditions to correlate their structure-activity relationship (SAR). Unlike, the free-base precursors, Zn(II) complexes of these nitroporphyrins displayed nearly complete inhibition in the entry of lentiviruses such as HIV-1 and SIVmac under non-photodynamic conditions. In addition, the Zn(II) complexes also exhibited a higher in vitro photodynamic activity towards human lung cancer cell-line A549 than their free-base precursors. Our results strongly suggest that incorporation of Zn(II) has improved the antiviral and anticancer properties of the nitroporphyrins. To the best of our knowledge, this is the first report demonstrating the dual activity of nitroporphyrin-zinc complexes as antiviral and anti-cancer, which will aid in their development as therapeutics in clinics.

G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry.

The high genetic diversity of Human Immunodeficiency virus (HIV), has hindered the development of effective vaccines or antiviral drugs against it. Hence, there is a continuous need for identification of new antiviral targets. HIV exploits specific host proteins also known as HIV-dependency factors during its replication inside the cell. Potassium channels play a crucial role in the life cycle of several viruses by modulating ion homeostasis, cell signaling, cell cycle, and cell death. In this study, using pharmacological tools, we have identified that HIV utilizes distinct cellular potassium channels at various steps in its life cycle. Members of inwardly rectifying potassium (Kir) channel family, G protein-coupled (GIRK), and ATP-sensitive (KATP) are involved in HIV entry. Blocking these channels using specific inhibitors reduces HIV entry. Another member, Kir 1.1 plays a role post entry as inhibiting this channel inhibits virus production and release. These inhibitors are not toxic to the cells at the concentration used in the study. We have further identified the possible mechanism through which these potassium channels regulate HIV entry by using a slow-response potential-sensitive probe DIBAC4(3) and have observed that blocking these potassium channels inhibits membrane depolarization which then inhibits HIV entry and virus release as well. These results demonstrate for the first time, the important role of Kir channel members in HIV-1 infection and suggest that these K+ channels could serve as a safe therapeutic target for treatment of HIV/AIDS.

Resistance to Second-Generation HIV-1 Maturation Inhibitors.

A betulinic acid-based compound, bevirimat (BVM), inhibits HIV-1 maturation by blocking a late step in protease-mediated Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. Previous studies showed that mutations conferring resistance to BVM cluster around the CA-SP1 cleavage site. Single amino acid polymorphisms in the SP1 region of Gag and the C terminus of CA reduced HIV-1 susceptibility to BVM, leading to the discontinuation of BVM's clinical development. We recently reported a series of "second-generation" BVM analogs that display markedly improved potency and breadth of activity relative to the parent molecule. Here, we demonstrate that viral clones bearing BVM resistance mutations near the C terminus of CA are potently inhibited by second-generation BVM analogs. We performed de novo selection experiments to identify mutations that confer resistance to these novel compounds. Selection experiments with subtype B HIV-1 identified an Ala-to-Val mutation at SP1 residue 1 and a Pro-to-Ala mutation at CA residue 157 within the major homology region (MHR). In selection experiments with subtype C HIV-1, we identified mutations at CA residue 230 (CA-V230M) and SP1 residue 1 (SP1-A1V), residue 5 (SP1-S5N), and residue 10 (SP1-G10R). The positions at which resistance mutations arose are highly conserved across multiple subtypes of HIV-1. We demonstrate that the mutations confer modest to high-level maturation inhibitor resistance. In most cases, resistance was not associated with a detectable increase in the kinetics of CA-SP1 processing. These results identify mutations that confer resistance to second-generation maturation inhibitors and provide novel insights into the mechanism of resistance.IMPORTANCE HIV-1 maturation inhibitors are a class of small-molecule compounds that block a late step in the viral protease-mediated processing of the Gag polyprotein precursor, the viral protein responsible for the formation of virus particles. The first-in-class HIV-1 maturation inhibitor bevirimat was highly effective in blocking HIV-1 replication, but its activity was compromised by naturally occurring sequence polymorphisms within Gag. Recently developed bevirimat analogs, referred to as "second-generation" maturation inhibitors, overcome this issue. To understand more about how these second-generation compounds block HIV-1 maturation, here we selected for HIV-1 mutants that are resistant to these compounds. Selections were performed in the context of two different subtypes of HIV-1. We identified a small set of mutations at highly conserved positions within the capsid and spacer peptide 1 domains of Gag that confer resistance. Identification and analysis of these maturation inhibitor-resistant mutants provide insights into the mechanisms of resistance to these compounds.

Role of APOBEC3 proteins in proteasome inhibitor-mediated reactivation of latent HIV-1 viruses.

Proteasome inhibitors (PIs) have been identified as an emerging class of HIV-1 latency-reversing agents (LRAs). These inhibitors can reactivate latent HIV-1 to produce non-infectious viruses. The mechanism underlying reduced infectivity of reactivated viruses is unknown. In this study, we analysed PI-reactivated viruses using biochemical and virological assays and demonstrated that these PIs stabilized the cellular expression of HIV-1 restriction factor, APOBEC3G, facilitating its packaging in the released viruses. Using infectivity assay and immunoblotting, we observed that the reduction in viral infectivity was due to enhanced levels of functionally active APOBEC3 proteins packaged in the virions. Sequencing of the proviral genome in the target cells revealed the presence of APOBEC3 signature hypermutations. Our study strengthens the role of PIs as bifunctional LRAs and demonstrates that the loss of infectivity of reactivated HIV-1 virions may be due to the increased packaging of APOBEC3 proteins in the virus.

Maturation inhibitors facilitate virus assembly and release of HIV-1 capsid P224 mutant.

HIV-1 Maturation inhibitors (MIs) bind to the C-terminal domain of capsid protein (CA-CTD) and spacer peptide 1 (SP1) in HIV-1 Gag and inhibit the CA-SP1 cleavage by stabilizing the immature Gag. The ß-turn motif, GVGGP in the HIV CA-CTD (residues 220-224) is one of the key determinants of HIV Gag assembly. In the present study, we mutated each residue of HIV-1 ß-turn motif to alanine and observed complete inhibition of virus release of all mutants. This defect in virus release was rescued in the presence of maturation inhibitors; BVM and PF-46396 for P224A mutant. To our knowledge, this is the first report of identification of BVM and PF-46396-dependent capsid mutant. Our results highlight the importance of the core ß-turn motif residues in immature virus assembly and suggest that the presence of MIs enhances Gag membrane binding and multimerization thereby restoring virus release of HIV Gag P224 mutant.

Human APOBEC3B interacts with the heterogenous nuclear ribonucleoprotein A3 in cancer cells.

Human APOBEC3B (A3B), like other APOBEC3 members, is a cytosine deaminase which causes hypermutation of single stranded genome. Recent studies have shown that A3B is predominantly elevated in multiple cancer tissues and cell lines such as the bladder, cervix, lung, head and neck, and breast. Upregulation and activation of A3B in developing tumors can cause an unexpected cluster of mutations which promote cancer development and progression. The cellular proteins which facilitate A3B function through direct or indirect interactions remain largely unknown. In this study, we performed LC-MS-based proteomics to identify cellular proteins which coimmunoprecipitated with A3B. Our results indicated a specific interaction of A3B with hnRNP A3 (heterogeneous nuclear ribonucleoprotein). This interaction was verified by co-immunoprecipitation and was found to be RNA-dependent. Furthermore, A3B and hnRNP A3 colocalized as evident from immunofluorescence analysis.

Novel host restriction factors implicated in HIV-1 replication.

Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

Insights into the activity of maturation inhibitor PF-46396 on HIV-1 clade C.

HIV maturation inhibitors are an emerging class of anti-retroviral compounds that inhibit the viral protease-mediated cleavage of the Gag, CA-SP1 (capsid-spacer peptide 1) peptide to mature CA. The first-in-class maturation inhibitor bevirimat (BVM) displayed potent activity against HIV-1 clade B but was ineffective against other HIV-1 clades including clade C. Another pyridone-based maturation inhibitor, PF-46396 displayed potent activity against HIV-1 clade B. In this study, we aimed at determining the activity of PF-46396 against HIV-1 clade C. We employed various biochemical and virological assays to demonstrate that PF-46396 is effective against HIV-1 clade C. We observed a dose dependent accumulation of CA-SP1 intermediate in presence of the compound. We carried out mutagenesis in the CA- SP1 region of HIV-1 clade C Gag and observed that the mutations conferred resistance against the compound. Many mutations inhibited Gag processing thereby reducing virus release in the absence of the compound. However, presence of PF-46396 rescued these defects and enhanced virus release, replication capacity and infectivity of HIV-1 clade C. These results put together identify PF-46396 as a broadly active maturation inhibitor against HIV-1 clade B and C and help in rational designing of novel analogs with reduced toxicity and increased efficacy for its potential use in clinics.

Immunoproteomic Analysis of Antibody Response of Rabbit Host Against Heat-Killed Francisella tularensis Live Vaccine Strain.

Francisella tularensis, the causative agent of tularemia, has attained the status of one of the high priority agents that could be used in the act of bioterrorism. Currently, there is no licensed vaccine for this highly infectious intracellular pathogen. Being a listed 'Category A' agent of the U.S. Center for Disease Control and Prevention (CDC), vaccines and therapeutics are immediately required against this pathogen. In this study, an immunoproteomic approach based on the techniques of 2-dimensional gel electrophoresis (2DE) and immunoblotting combined with mass spectrometry (MS) was used for elucidation of immunogenic components and putative vaccine candidates. Whole-cell soluble protein extract of F. tularensis LVS (Ft LVS) was separated by 2DE, and immunoblots were developed with sera raised in rabbit after immunization with heat-killed Ft LVS. A total of 28 immunoreactive proteins were identified by tandem mass spectrometry. Rabbit immunoproteome of F. tularensis was compared with those previously reported using sera from human patients and in murine model. Out of 28 immunoreactive proteins identified in this study, 12 and 17 overlapping proteins were recognized by human and murine sera, respectively. Nine proteins were found immunogenic in all the three hosts, while eight new immunogenic proteins were found in this study. Identified immunoreactive proteins may find application in design and development of protein subunit vaccine for tularemia.

Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.

Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.