Recent advancement of autophagy in polyploid giant cancer cells and its interconnection with senescence and stemness for therapeutic opportunities.

Recurrent chemotherapy-induced senescence and resistance are attributed to the polyploidization of cancer cells that involve genomic instability and poor prognosis due to their unique form of cellular plasticity. Autophagy, a pre-dominant cell survival mechanism, is crucial during carcinogenesis and chemotherapeutic stress, favouring polyploidization. The selective autophagic degradation of essential proteins associated with cell cycle progression checkpoints deregulate mitosis fidelity and genomic integrity, imparting polyploidization of cancer cells. In connection with cytokinesis failure and endoreduplication, autophagy promotes the formation, maintenance, and generation of the progeny of polyploid giant cancer cells. The polyploid cancer cells embark on autophagy-guarded elevation in the expression of stem cell markers, along with triggered epithelial and mesenchymal transition and senescence. The senescent polyploid escapers represent a high autophagic index than the polyploid progeny, suggesting regaining autophagy induction and subsequent autophagic degradation, which is essential for escaping from senescence/polyploidy, leading to a higher proliferative phenotypic progeny. This review documents the various causes of polyploidy and its consequences in cancer with relevance to autophagy modulation and its targeting for therapeutic intervention as a novel therapeutic strategy for personalized and precision medicine.

Imperative connotation of SODs in cancer: Emerging targets and multifactorial role of action.

Superoxide dismutase (SOD) is a crucial enzyme responsible for the redox homeostasis inside the cell. As a part of the antioxidant defense system, it plays a pivotal role in the dismutation of the superoxide radicals ( O 2 - $$ {{\mathrm{O}}_2}^{-} $$ ) generated mainly by the oxidative phosphorylation, which would otherwise bring out the redox dysregulation, leading to higher reactive oxygen species (ROS) generation and, ultimately, cell transformation, and malignancy. Several studies have shown the involvement of ROS in a wide range of human cancers. As SOD is the key enzyme in regulating ROS, any change, such as a transcriptional change, epigenetic remodeling, functional alteration, and so forth, either activates the proto-oncogenes or aberrant signaling cascades, which results in cancer. Interestingly, in some cases, SODs act as tumor promoters instead of suppressors. Furthermore, SODs have also been known to switch their role during tumor progression. In this review, we have tried to give a comprehensive account of SODs multifactorial role in various human cancers so that SODs-based therapeutic strategies could be made to thwart cancers.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes resulting in reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral cancer.

A Novel Phytocolorant, Neoxanthin, as a Potent Chemopreventive: Current Progress and Future Prospects.

Cancer is a general term for a group of similar diseases. It is a combined process that results from an accumulation of abnormalities at different biological levels, which involves changes at both genetic and biochemical levels in the cells. Several modifiable risk factors for each type of cancer include heredity, age, and institutional screening guidelines, including colonoscopy, mammograms, prostate-specific antigen testing, etc., which an individual cannot modify. Although a wide range of resources is available for cancer drugs and developmental studies, the cases are supposed to increase by about 70% in the next two decades due to environmental factors commonly driven by the way of living. The drugs used in cancer prevention are not entirely safe, have potential side effects and are generally unsuitable owing to substantial monetary costs. Interventions during the initiation and progression of cancer can prevent, diminish, or stop the transformation of healthy cells on the way to malignancy. Diet modifications are one of the most promising lifestyle changes that can decrease the threat of cancer development by nearly 40%. Neoxanthin is a xanthophyll pigment found in many microalgae and macroalgae, having significant anti-cancer, antioxidant and chemo-preventive activity. In this review, we have focused on the anti-cancer activity of neoxanthin on different cell lines and its cancer-preventive activity concerning obesity and oxidative stress. In addition to this, the preclinical studies and future perspectives are also discussed in this review.

SIRT1 inhibits mitochondrial hyperfusion associated mito-bulb formation to sensitize oral cancer cells for apoptosis in a mtROS-dependent signalling pathway.

SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III histone deacetylase acting as a tumor suppressor gene, is downregulated in oral cancer cells. Non-apoptotic doses of cisplatin (CDDP) downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks. The hyperfused mitochondrial networks preserve the release of cytochrome C (CYCS) by stabilizing the mitochondrial inner membrane cristae (formation of mitochondrial nucleoid clustering mimicking mito-bulb like structures) and reducing the generation of mitochondrial superoxide to inhibit apoptosis. Overexpression of SIRT1 reverses the mitochondrial hyperfusion by initiating DNM1L-regulated mitochondrial fission. In the overexpressed cells, inhibition of mitochondrial hyperfusion and nucleoid clustering (mito-bulbs) facilitates the cytoplasmic release of CYCS along with an enhanced generation of mitochondrial superoxide for the subsequent induction of apoptosis. Further, low-dose priming with gallic acid (GA), a bio-active SIRT1 activator, nullifies CDDP-mediated apoptosis inhibition by suppressing mitochondrial hyperfusion. In this setting, SIRT1 knockdown hinders apoptosis activation in GA-primed oral cancer cells. Similarly, SIRT1 overexpression in the CDDP resistance oral cancer-derived polyploid giant cancer cells (PGCCs) re-sensitizes the cells to apoptosis. Interestingly, synergistically treated with CDDP, GA induces apoptosis in the PGCCs by inhibiting mitochondrial hyperfusion.

Algal-derived nanoparticles and their antibacterial potential: Current evidence and future prospectives.

Green nanotechnology provides efficient solutions for converting biological systems to green approaches through nanomaterial synthesis and thus preventing any associated toxicity. Green nanoparticle (NP) synthesis involves the use of biological sources for synthesis of metallic NPs for pharmaceutical and biomedical applications in an eco-friendly and comparatively economical manner. Nanotechnology is a promising technology with a wide range of pharmaceutical applications in the modern world because it provides a higher surface area (SA) to volume (Vol) ratio. Compared to chemically synthesized NPs, algal-based NPs have recently received increasing attention from researchers worldwide as potential agents to treat and inhibit infections caused by microbial pathogens resistant to antibiotics. Algae produce various bioactive compounds such as chlorophyll, phycobilins, phenolics, flavonoids, glucosides, tannins, and saponins that can be used as therapeutic agents. Metallic NPs exert greater toxic effects on their targets than their macroscopic counterparts. Both macroalgae and some microalgae are used to synthesize metallic NPs that exhibit antimicrobial activity. The synthesis of algal-based NPs may provide potential drug candidates for use in nanomedicine against microbial diseases. To date, many studies have been conducted on algal-based NPs and their potential antimicrobial and antifungal activities. Therefore, in this review we have focused on the green synthesis of different NPs using algae and their therapeutic potential with reference to their antimicrobial activity.

Co-targeting autophagy and NRF2 signaling triggers mitochondrial superoxide to sensitize oral cancer stem cells for cisplatin-induced apoptosis.

Cancer stem cell (CSC) populations are regulated by autophagy, which in turn modulates tumorigenicity and malignancy. In this study, we demonstrated that cisplatin treatment enriches the CSCs population by increasing autophagosome formation and speeding up autophagosome-lysosome fusion by recruiting RAB7 to autolysosomes. Further, cisplatin treatment stimulates lysosomal activity and increases autophagic flux in oral CD44+ cells. Interestingly, both ATG5- and BECN1-dependent autophagy are essential for maintaining cancer stemness, self-renewal, and resistance to cisplatin-induced cytotoxicity in oral CD44+ cells. Moreover, we discovered that autophagy-deficient (shATG5 and/or shBECN1) CD44+ cells activates nuclear factor, erythroid 2 like 2 (NRF2) signaling, which in turn reduces the elevated reactive oxygen species (ROS) level enhancing cancer stemness. Genetic inhibition of NRF2 (siNRF2) in autophagy-deficient CD44+ cells increases mitochondrial ROS (mtROS) level, reducing cisplatin-resistance CSCs, and pre-treatment with mitoTEMPO [a mitochondria-targeted superoxide dismutase (SOD) mimetic] lessened the cytotoxic effect enhancing cancer stemness. We also found that inhibiting autophagy (with CQ) and NRF2 signaling (with ML-385) combinedly increases cisplatin cytotoxicity, thereby suppressing the expansion of oral CD44+ cells; this finding has the potential to be clinically applicable in resolving CSC-associated chemoresistance and tumor relapse in oral cancer.

The inner mitochondrial membrane fission protein MTP18 serves as a mitophagy receptor to prevent apoptosis in oral cancer.

MTP18 (also known as MTFP1), an inner mitochondrial membrane protein, plays a vital role in maintaining mitochondrial morphology by regulating mitochondrial fission. Here, we found that MTP18 functions as a mitophagy receptor that targets dysfunctional mitochondria into autophagosomes for elimination. Interestingly, MTP18 interacts with members of the LC3 (also known as MAP1LC3) family through its LC3-interacting region (LIR) to induce mitochondrial autophagy. Mutation in the LIR motif (mLIR) inhibited that interaction, thus suppressing mitophagy. Moreover, Parkin or PINK1 deficiency abrogated mitophagy in MTP18-overexpressing human oral cancer-derived FaDu cells. Upon exposure to the mitochondrial oxidative phosphorylation uncoupler CCCP, MTP18[mLIR]-FaDu cells showed decreased TOM20 levels without affecting COX IV levels. Conversely, loss of Parkin or PINK1 resulted in inhibition of TOM20 and COX IV degradation in MTP18[mLIR]-FaDu cells exposed to CCCP, establishing Parkin-mediated proteasomal degradation of outer mitochondrial membrane as essential for effective mitophagy. We also found that MTP18 provides a survival advantage to oral cancer cells exposed to cellular stress and that inhibition of MTP18-dependent mitophagy induced cell death in oral cancer cells. These findings demonstrate that MTP18 is a novel mitophagy receptor and that MTP18-dependent mitophagy has pathophysiologic implications for oral cancer progression, indicating inhibition of MTP18-mitophagy could thus be a promising cancer therapy strategy.

Targeting SIRT1-regulated autophagic cell death as a novel therapeutic avenue for cancer prevention.

Cellular localization and deacetylation activity of sirtuin 1 (SIRT1) has a significant role in cancer regulation. The multifactorial role of SIRT1 in autophagy regulates several cancer-associated cellular phenotypes, aiding cellular survival and cell death induction. SIRT1-mediated deacetylation of autophagy-related genes (ATGs) and associated signaling mediators control carcinogenesis. The hyperactivation of bulk autophagy, disrupted lysosomal and mitochondrial biogenesis, and excessive mitophagy are key mechanism for SIRT1-mediated autophagic cell death (ACD). In terms of the SIRT1-ACD nexus, identifying SIRT1-activating small molecules and understanding the possible mechanism triggering ACD could be a potential therapeutic avenue for cancer prevention. In this review, we provide an update on the structural and functional intricacy of SIRT1 and SIRT1-mediated autophagy activation as an alternative cell death modality for cancer prevention.

CLU (clusterin) promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis to maintain SOX2-mediated stemness in oral cancer stem cells.

Mitophagy regulates cancer stem cell (CSC) populations affecting tumorigenicity and malignancy in various cancer types. Here, we report that cisplatin treatment led to the activation of higher mitophagy through regulating CLU (clusterin) levels in oral CSCs. Moreover, both the gain-of-function and loss-of-function of CLU indicated its mitophagy-specific role in clearing damaged mitochondria. CLU also regulates mitochondrial fission by activating the Ser/Thr kinase AKT, which triggered phosphorylation of DNM1L/Drp1 at the serine 616 residue initiating mitochondrial fission. More importantly, we also demonstrated that CLU-mediated mitophagy positively regulates oral CSCs through mitophagic degradation of MSX2 (msh homeobox 2), preventing its nuclear translocation from suppressing SOX2 activity and subsequent inhibition of cancer stemness and self-renewal ability. However, CLU knockdown disturbed mitochondrial metabolism generating excessive mitochondrial superoxide, which improves the sensitivity to cisplatin in oral CSCs. Notably, our results showed that CLU-mediated cytoprotection relies on SOX2 expression. SOX2 inhibition through genetic (shSOX2) and pharmacological (KRX-0401) strategies reverses CLU-mediated cytoprotection, sensitizing oral CSCs toward cisplatin-mediated cell death.

Seaweed-Derived Sulfated Polysaccharides; The New Age Chemopreventives: A Comprehensive Review.

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such as control of ROS generation and preservation of essential cell survival and death processes, sulfated polysaccharides' antioxidant and immunomodulatory potentials contribute to their disease-preventive effectiveness. Sulfated polysaccharides provide low cytotoxicity and good efficacy therapeutic outcomes via dynamic modulation of apoptosis in cancer. Understanding how sulfated polysaccharides affect human cancer cells and their molecular involvement in cell death pathways will showcase a new way of chemoprevention. In this review, the significance of apoptosis and autophagy-modulating sulfated polysaccharides has been emphasized, as well as the future direction of enhanced nano-formulation for greater clinical efficacy. Moreover, this review focuses on the recent findings about the possible mechanisms of chemotherapeutic use of sulfated polysaccharides, their potential as anti-cancer drugs, and proposed mechanisms of action to drive apoptosis in diverse malignancies. Because of their unique physicochemical and biological properties, sulfated polysaccharides are ideal for their bioactive ingredients, which can improve function and application in disease. However, there is a gap in the literature regarding the physicochemical properties and functionalities of sulfated polysaccharides and the use of sulfated polysaccharide-based delivery systems in functional cancer. Furthermore, the preclinical and clinical trials will reveal the drug's efficacy in cancer.

Autophagy for secretory protein: Therapeutic targets in cancer.

Autophagy, a classical cellular degradative catabolic process, also involves a functionally discrete non-degradative role in eukaryotic cells. It imparts critical regulatory function on conventional and unconventional protein secretion (degradative and secretory autophagy with distinct lysosomal degradation and extracellular expulsion, respectively) pathways. The N-amino terminal leader sequence containing proteins follows a conventional secretion pathway, while the leader-less proteins opt for secretory autophagy. The secretory autophagic process ensembles core autophagy machinery proteins, specifically ULK1/2, Beclin 1, LC3, and GABARAP, in coordination with Golgi re-assembly and stacking proteins (GRASPs). The secretory omegasomes fuse with the plasma membrane for the expulsion of cytosolic cargos to the extracellular environment. Alternatively, the secretory omegasomes also fuse with multi-vesicular bodies (MVBs) and harmonize ESCRTs (Complex I; TSG101) and Rab GTPase for their release to extracellular space. Autophagy has been associated with the secretion of diverse proteins involved in cellular signaling, inflammation, and carcinogenesis. Secreted proteins play an essential role in cancer by sustaining cell proliferation, inhibiting apoptosis, enhancing angiogenesis and metastasis, immune cell regulation, modulation of cellular energy metabolism, and resistance to anticancer drugs. The complexity of autophagy regulation during tumorigenesis is dependent on protein secretion pathways. Autophagy-regulated TOR-autophagy spatial coupling compartment complex energizes enhanced secretion of pro-inflammatory cytokines and leaderless proteins such as HMGB1. In conclusion, the chapter reviews the role of autophagy in regulating conventional and unconventional protein secretion pathways and its possible role in cancer.

Lysosome signaling in cell survival and programmed cell death for cellular homeostasis.

Recent developments in lysosome biology have transformed our view of lysosomes from static garbage disposals that can also act as suicide bags to decidedly dynamic multirole adaptive operators of cellular homeostasis. Lysosome-governed signaling pathways, proteins, and transcription factors equilibrate the rate of catabolism and anabolism (autophagy to lysosomal biogenesis and metabolite pool maintenance) by sensing cellular metabolic status. Lysosomes also interact with other organelles by establishing contact sites through which they exchange cellular contents. Lysosomal function is critically assessed by lysosomal positioning and motility for cellular adaptation. In this setting, mechanistic target of rapamycin kinase (MTOR) is the chief architect of lysosomal signaling to control cellular homeostasis. Notably, lysosomes can orchestrate explicit cell death mechanisms, such as autophagic cell death and lysosomal membrane permeabilization-associated regulated necrotic cell death, to maintain cellular homeostasis. These lines of evidence emphasize that the lysosomes serve as a central signaling hub for cellular homeostasis.

Microalgal Phycoremediation: A Glimpse into a Sustainable Environment.

Microalgae are continually exposed to heavy metals and metalloids (HMMs), which stifles their development and reproduction due to the resulting physiological and metabolic abnormalities, leading to lower crop productivity. They must thus change their way of adapting to survive in such a hostile environment without sacrificing their healthy growth, development, reproductive capacity, or survival. The mode of adaptation involves a complex relationship of signalling cascades that govern gene expression at the transcriptional and post-transcriptional levels, which consequently produces altered but adapted biochemical and physiochemical parameters. Algae have been reported to have altered their physicochemical and molecular perspectives as a result of exposure to a variety of HMMs. Hence, in this review, we focused on how microalgae alter their physicochemical and molecular characteristics as a tolerance mechanism in response to HMM-induced stress. Furthermore, physiological and biotechnological methods can be used to enhance extracellular absorption and clean up. The introduction of foreign DNA into microalgae cells and the genetic alteration of genes can boost the bio-accumulation and remediation capabilities of microalgae. In this regard, microalgae represent an excellent model organism and could be used for HMM removal in the near future.

Epigenetic dysregulation in autophagy signaling as a driver of viral manifested oral carcinogenesis.

BACKGROUND: Concurrent viral infections insist on dysregulated epigenetics of tumor suppressor genes (TSGs), cell cycle regulators, apoptosis, and autophagy-associated genes to manifest oral carcinogenesis. Autophagy has been projected as a strategic defense signaling cascade against viral entry and subsequent oral carcinogenesis. Compromised autophagy signaling during viral infection fuels oral cancer initiation and progression. SCOPE OF REVIEW: The aberrant expression of autophagy genes and their encoded proteins is catalyzed by the dysregulated epigenome, legitimate epigenomic mutations, and post-transcriptional modifications such as hypermethylation, deacetylation of histone and non-histone targets, and hyperacetylation of histones that drive malignant transformation during oral carcinogenesis. Recent investigations have predicted epi-drugs (intriguingly methylation and deacetylation inhibitors and activators) as next-generation oral cancer therapeutic agents with a special notation for autophagy regulation. MAJOR CONCLUSIONS: This review focuses on the epigenetic mediated post-transcriptional modulation of autophagy genes during viral manifested oral carcinogenesis with a distinctive perception of autophagy-modulating epi-drugs in oral cancer therapeutics.

MTP18 inhibition triggers mitochondrial hyperfusion to induce apoptosis through ROS-mediated lysosomal membrane permeabilization-dependent pathway in oral cancer.

Although stress-induced mitochondrial hyperfusion (SIMH) exerts a protective role in aiding cell survival, in the absence of mitochondrial fission, SIMH drives oxidative stress-related induction of apoptosis. In this study, our data showed that MTP18, a mitochondrial fission-promoting protein expression, was increased in oral cancer. We have screened and identified S28, a novel inhibitor of MTP18, which was found to induce SIMH and subsequently trigger apoptosis. Interestingly, it inhibited MTP18-mediated mitochondrial fission, as shown by a decrease in p-Drp1 along with increased Mfn1 expression in oral cancer cells. Moreover, S28 induced autophagy but not mitophagy due to the trouble in engulfment of hypoperfused mitochondria. Interestingly, S28-mediated SIMH resulted in the loss of mitochondrial membrane potential, leading to the consequent generation of mitochondrial superoxide to induce intrinsic apoptosis. Mechanistically, S28-induced mitochondrial superoxide caused lysosomal membrane permeabilization (LMP), resulting in decreased lysosomal pH, which impaired autophagosome-lysosome fusion. In this setting, it showed that overexpression of MTP18 resulted in mitochondrial fission leading to mitophagy and inhibition of superoxide-mediated LMP and apoptosis. Further, S28, in combination with FDA-approved anticancer drugs, exhibited higher apoptotic activity and decreased cell viability, suggesting the MTP18 inhibition combined with the anticancer drug could have greater efficacy against cancer.

Algal Phlorotannins as Novel Antibacterial Agents with Reference to the Antioxidant Modulation: Current Advances and Future Directions.

The increasing drug resistance of infectious microorganisms is considered a primary concern of global health care. The screening and identification of natural compounds with antibacterial properties have gained immense popularity in recent times. It has previously been shown that several bioactive compounds derived from marine algae exhibit antibacterial activity. Similarly, polyphenolic compounds are generally known to possess promising antibacterial capacity, among other capacities. Phlorotannins (PTs), an important group of algae-derived polyphenolic compounds, have been considered potent antibacterial agents both as single drug entities and in combination with commercially available antibacterial drugs. In this context, this article reviews the antibacterial properties of polyphenols in brown algae, with particular reference to PTs. Cell death through various molecular modes of action and the specific inhibition of biofilm formation by PTs were the key discussion of this review. The synergy between drugs was also discussed in light of the potential use of PTs as adjuvants in the pharmacological antibacterial treatment.

A state-of-the-art review on fucoidan as an antiviral agent to combat viral infections.

As a significant public health hazard with several drug side effects during medical treatment, searching for novel therapeutic natural medicines is promising. Sulfated polysaccharides from algae, such as fucoidan, have been discovered to have a variety of medical applications, including antibacterial and immunomodulatory properties. The review emphasized on the utilization of fucoidan as an antiviral agent against viral infections by inhibiting their attachment and replication. Moreover, it can also trigger immune response against viral infection in humans. This review suggested to be use the fucoidan for the potential protective remedy against COVID-19 and addressing the antiviral activities of sulfated polysaccharide, fucoidan derived from marine algae that could be used as an anti-COVID19 drug in near future.

Low-dose priming of gamma radiation enhanced cadmium tolerance in Chlamydomonas reinhardtii by modulating physio-biochemical pathways.

Microalgae are natural biotic models for exploring the genotoxic effect of heavy metals, irradiation, other external stimuli and the toxicant elimination. The effective removal of heavy metals from the aquatic environment using microalgae has gained considerable attention. However, limited research was carried out on cadmum toxicity in microalgae and their use as bio-accumulants. Previous research suggested that low-dose priming with non-ionizing radiations, such as gamma radiation, increased heavy metal tolerance in plants and aquatic photosynthetic microalgae. In the present study, we have hypothesized the growth inhibitory physiochemical properties of cadmium (Cd) in Chlamydomonas reinhardtii, and analyzed the protective role of low-dose gamma radiations priming against Cd-induced growth inhibition by emphasizing mechanism of cell survival by antioxidant defence system. Experimentally, the gamma-primed C. reinhardtii exhibited higher cell survival and Cd tolerance with effective modulation of biochemical responses such as antioxidant enzymes. The current investigation revealed that low-dose priming of gamma radiation masks Cd-mediated oxidative stress and enhances cellular detoxification via intracellular antioxidant enzymes in C. reinhardtii.

Cyanobacteria and Algae-Derived Bioactive Metabolites as Antiviral Agents: Evidence, Mode of Action, and Scope for Further Expansion; A Comprehensive Review in Light of the SARS-CoV-2 Outbreak.

COVID-19-a severe acute respiratory syndrome disease caused by coronavirus 2 (SARS-CoV-2)-has recently attracted global attention, due to its devastating impact, to the point of being declared a pandemic. The search for new natural therapeutic drugs is mandatory, as the screening of already-known antiviral drugs so far has led to poor results. Several species of marine algae have been reported as sources of bioactive metabolites with potential antiviral and immunomodulatory activities, among others. Some of these bioactive metabolites might be able to act as antimicrobial drugs and also against viral infections by inhibiting their replication. Moreover, they could also trigger immunity against viral infection in humans and could be used as protective agents against COVID-In this context, this article reviews the main antiviral activities of bioactive metabolites from marine algae and their potential exploitation as anti-SARS-CoV-2 drugs.