Embodiments for the synthesis of sensitive oligonucleotides as well as insensitive oligonucleotides are provided. Sulfur-based groups are used for the protection of exo-amino groups of nucleobases, phosphate groups and 2′-OH groups, and as cleavable linker for linking oligonucleotides to a support. Oligonucleotide syntheses are achieved under typical conditions using phosphoramidite chemistry with important modifications. To prevent replacing sulfur-based protecting groups by acyl groups via cap-exchange, special capping agents are used. To retain hydrophobic tag to assist RP HPLC purification, special phosphoramidites are used in the last synthetic cycle. With the sulfur-based groups for protection and linking, oligonucleotide deprotection and cleavage are achieved via oxidation followed by beta-elimination under mild conditions. Therefore, besides for insensitive oligonucleotide synthesis, the embodiments of the invention are capable for the synthesis of oligonucleotide analogs containing sensitive functional groups that cannot survive the harsh conditions used in prior art oligonucleotide synthesis technologies.

Provided herein are novel synthetic routes to amines through an oxime intermediate, e.g., 3′-N nucleosides and novel and intermediate compounds produced during these synthetic procedures.

Provided for herein is a method for detecting the presence of a nucleic acid target molecule in a biological sample. In certain aspects, the method comprises contacting a test sample that comprises (i) a biological sample comprising a nucleic acid target molecule and (ii) an osmylated single-stranded oligonucleotide probe comprising at least one pyrimidine residue covalently bonded to a substituted or unsubstituted Osmium tetroxide (OsO.sub.4)-2,2′-bypyridine group (OsBp group).

Provided for herein is a method for detecting the presence of a nucleic acid target molecule in a biological sample. In certain aspects, the method comprises contacting a test sample that comprises (i) a biological sample comprising a nucleic acid target molecule and (ii) an osmylated single-stranded oligonucleotide probe comprising at least one pyrimidine residue covalently bonded to a substituted or unsubstituted Osmium tetroxide (OsO.sub.4)-2,2′-bypyridine group (OsBp group).

Linker compounds, methods of making them, and methods of using them as linking agents for oligonucleotides and other chemical and biological substances are described. Embodiments of linker compounds are configured or selected to exhibit higher stability to cleavage by serum nucleases relative to intracellular nucleases, enabling enhanced control of longevity and hence bioavailability to a target cell of the chemical and biological substances linked together by such linker compounds when administered to a subject.

The present invention provides an amino acid composition, and a method for producing amino acids by means of energy irradiation, the method comprises contacting a nanostructure catalyst with at least one nitrogen-containing source, at least one hydrogen-containing source and at least one carbon-containing source, and irradiating the nanostructure catalyst, the nitrogen-containing source, the hydrogen-containing source and the carbon-containing source with energy, to produce the amino acids.

The present invention provides an amino acid composition, and a method for producing amino acids by means of energy irradiation, the method comprises contacting a nanostructure catalyst with at least one nitrogen-containing source, at least one hydrogen-containing source and at least one carbon-containing source, and irradiating the nanostructure catalyst, the nitrogen-containing source, the hydrogen-containing source and the carbon-containing source with energy, to produce the amino acids.

The present disclosure provides modified oligonucleotides and compositions and methods thereof. In some embodiments, provided technologies comprise modified sugars and/or modified internucleotidic linkages. In some embodiments, the present disclosure provides technologies for preparing modified oligonucleotides. In some embodiments, the present disclosure provides chirally controlled oligonucleotide compositions and methods for their preparation and uses.

Provided is a method of treating a disease caused by a nidovirus that encodes Nsp15, such as a coronavirus, an arterivirus, or a torovirus, in a subject in need thereof comprising administering a therapeutically effective amount of an active agent selected from 3′-uridylic acid, 5′-uridylic acid, citrate, methacycline, meclocycline sulfosalicylate, mitoxantrone, epirubicin hydrochloride, daunorubicin hydrochloride, sorafenib, sunitinib malate, primaquine diphosphate, closantel, isopropyl ester of N4-hydroxycytidine, GpU dinucleotide or derivatives thereof, and tipiracil or N-substituted derivatives thereof. Further provided are a method of inhibiting an Nsp15 endoribonuclease of a nidovirus that encodes Nsp15 and compounds of formulas (I′) and (II′).

A method for detecting nucleic acids by (a) providing a sample having target nucleic acids, each nucleic acid having contiguous first, second, and third domains; (b) contacting the sample with probe sets to form hybridization complexes, wherein each probe set includes (i) a first probe having a sequence that is complementary to the first domain; and (ii) a second probe having a sequence substantially complementary to the third domain; (c) extending the first probes along the second domains of the complexes while the complexes are immobilized on a solid support; (d) ligating the extended first probes to the second probes to form templates; (e) amplifying the templates with primers that are complementary to the first and second priming sequences to produce amplicons; and (f) detecting the amplicons on the surface of a nucleic acid array.