No abstract

Phishing is an online criminal act that occurs when a malicious webpage impersonates as legitimate webpage so as to acquire sensitive information from the user. Phishing attack continues to pose a serious risk for web users and annoying threat within the field of electronic commerce. This paper focuses on discerning the significant features that discriminate between legitimate and phishing URLs. These features are then subjected to associative rule mining—apriori and predictive apriori. The rules obtained are interpreted to emphasize the features that are more prevalent in phishing URLs. Analyzing the knowledge accessible on phishing URL and considering confidence as an indicator, the features like transport layer security, unavailability of the top level domain in the URL and keyword within the path portion of the URL were found to be sensible indicators for phishing URL. In addition to this number of slashes in the URL, dot in the host portion of the URL and length of the URL are also the key factors for phishing URL.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5= untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5= UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5= cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NPmediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus.IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5= UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease.KEYWORDS bunyavirus, negative-strand RNA virus, nucleocapsid protein, translation C rimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus within the Bunyaviridae family that causes severe hemorrhagic fever with a mortality rate of 30% in more than 30 countries worldwide (1-4). There is no vaccine against CCHFV, and therapeutic interventions are limited. This virus is transmitted to humans by either tick bites or direct contact with blood or tissue samples from the infected hosts (5, 6). The recent frequent outbreaks of CCHFV in Mediterranean countries are likely associated with the broad habitat and population size of the CCHFV tick vector (7). The increased tick vector population could be associated with climate change (7). The CCHFV genome is composed of three negative-sense RNA segments (S, M, and L), which encode nucleocapsid protein (NP), glycoprotein precursor (GPC), and RNA-dependent RNA polymerase (RdRp), respectively (8). Although NP is mainly considered to be an integral component of the viral capsid, recent studies on Lassa fever virus (LASV) (Arenaviridae)

Crimean Congo hemorrhagic fever, a zoonotic viral disease, has high mortality rate in humans. There is currently no vaccine for Crimean Congo hemorrhagic fever virus (CCHFV) and chemical interventions are limited. The three negative sense genomic RNA segments of CCHFV are specifically encapsidated by the nucleocapsid protein into three ribonucleocapsids, which serve as templates for the viral RNA dependent RNA polymerase. Here we demonstrate that CCHFV nucleocapsid protein has two distinct binding modes for double and single strand RNA. In the double strand RNA binding mode, the nucleocapsid protein preferentially binds to the vRNA panhandle formed by the base pairing of complementary nucleotides at the 5’ and 3’ termini of viral genome. The CCHFV nucleocapsid protein does not have RNA helix unwinding activity and hence does not melt the duplex vRNA panhandle after binding. In the single strand RNA binding mode, the nucleocapsid protein does not discriminate between viral and non-viral RNA molecules. Binding of both vRNA panhandle and single strand RNA induce a conformational change in the nucleocapsid protein. Nucleocapsid protein remains in a unique conformational state due to simultaneously binding of structurally distinct vRNA panhandle and single strand RNA substrates. Although the role of dual RNA binding modes in the virus replication cycle is unknown, their involvement in the packaging of viral genome and regulation of CCHFV replication in conjunction with RdRp and host derived RNA regulators is highly likely.

An evolutionarily conserved sequence at the 5' terminus of hantaviral genomic RNA plays an important role in viral transcription initiation and packaging of the viral genome into viral nucleocapsids. Interaction of viral nucleocapsid protein (N) with this conserved sequence facilitates mRNA translation by a unique N-mediated translation strategy. Whereas this evolutionarily conserved sequence facilitates virus replication with the assistance of N in eukaryotic hosts having multifaceted antiviral defense, we demonstrate its interaction with N presents a novel target for therapeutic intervention of hantavirus disease. Using a high throughput screening approach, we identified three lead inhibitors that bind and induce structural perturbations in N. The inhibitors interrupt N-RNA interaction and abrogate both viral genomic RNA synthesis and N-mediated translation strategy without affecting the canonical translation machinery of the host cell. The inhibitors are well tolerated by cells and inhibit hantavirus replication with the same potency as ribavarin, a commercially available antiviral. We report the identification of a unique chemical scaffold that disrupts a critical RNA-protein interaction in hantaviruses and holds promise for the development of the first anti-hantaviral therapeutic with broad spectrum antiviral activity.